the compounds useful in this invention are prepared following procedures previously disclosed in u . s . pat . nos . 3 , 419 , 559 ; 3 , 455 , 941 ; 3 , 457 , 267 ; 3 , 513 , 236 and 4 , 886 , 794 and in j . pharm . sci . 58 ( 3 ), 362 - 364 and are hereby incorporated by reference . the invention compounds are prepared according to scheme a . ## str7 ## this reaction is typically performed using a polar solvent such as ethanol , butanol , or dimethyl formamide at or near the boiling point of the solvent with an acid acceptor such as sodium carbonate , potassium carbonate or sodium bicarbonate present . potassium iodide may be used to catalyze the reaction . the product is isolated and purified by conventional methods . scheme b indicates the reaction used to obtain the alkenyloxy substituted invention compounds . ## str8 ## the 5 - haloalkyl - 2 - oxazolidinones are obtained from the appropriate n - substituted aminomethyltetrahydrofuran or the corresponding tetrahydropyran according to scheme c . ## str9 ## this ring - opening / ring closure reaction is carried out in an aprotic solvent at or below ambient temperature . the precursor substituted aminomethyltetrahydrofuran or pyran are prepared from the commercially available 2 -( chloromethyl ) tetrahydrofuran or pyran and the desired amine as shown in scheme d . ## str10 ## excess amine serves as the solvent in the procedure of scheme d . the above procedures are broadly described and actual reaction conditions will depend on the reaction temperatures , solvents , purity of reactants and the like . the following preparations and examples are illustrative of the above reaction schemes and should not be construed as limiting to this disclosure in any way . reactants for which no preparative procedure is given are either commercially available or readily prepared using published procedures . it is expected that one skilled in the art would be able to carry out this invention without undue experimentation . a solution of 2 -( bromomethyl ) tetrahydro - 2h - pyran ( 100 g , 0 . 558 mol ) and isopropylamine ( 66 . 0 g , 1 . 12 mol ) was refluxed under nitrogen overnight , and the solvent was removed under reduced pressure . a 3n hydrochloric acid solution was added to acidify the residue , and the solution was washed twice with ether and made basic with a 50 % sodium hydroxide solution . the product was extracted twice into ether , and the combined extracts were washed twice with a saturated sodium chloride solution , dried ( sodium sulfate ), filtered , and evaporated under reduced pressure to an oil ( 54 . 8 g , 62 % yield ). a portion of the oil ( 13 . 7 g , 0 . 0873 mol ) was dissolved in warm 2 - propanol and a solution of oxalic acid ( 7 . 86 g , 0 . 0873 mol ) in warm 2 - propanol was added . a solid precipitated , which was collected by filtration and dried under high vacuum at 60 ° c . to give 17 . 24 g , mp 172 °- 175 ° c . analysis : calculated for c 11 h 12 no 8 : c , 53 . 43 ; h , 8 . 56 ; n , 5 . 66 ; found : c , 53 . 54 ; h , 8 , 94 ; n , 5 . 60 . a mixture of 2 -( bromomethyl ) tetrahydro - 2h - pyran ( 100 g , 0 . 558 mol ) and aniline ( 155 . 96 g , 1 . 67 mol ) was heated at 100 ° c . under nitrogen overnight and cooled to room temperature . a 3n hydrochloric acid solution ( 400 ml ) was added and the aqueous layer was washed three times with isopropyl ether . the aqueous layer was made basic with 50 % sodium hydroxide solution , and the product was extracted three times into isopropyl ether . the combined organic extracts were washed once with water and evaporated under reduced pressure . the resulting oil was poured into water ( 1400 ml ) and stirred . the water was decanted and water ( 1500 ml ) was again added . the aqueous layer was again decanted and the oil was triturated again in water ( 1500 ml ) to give a solid , which was recrystallized from methanol / water and dried under high vacuum to give 78 . 5 g of product containing one mole of water ( 67 % yield ). a 2 . 0 g portion was recrystallized from methanol / water and dried under high vacuum to give 0 . 71 g , mp 55 °- 58 ° c . analysis : calculated for c 12 h 17 no : c , 75 . 35 ; h , 8 , 96 ; n , 7 . 32 ; found : c , 75 . 33 ; h , 9 . 15 ; n , 7 . 25 . a mixture of tetrahydrofurfuryl chloride ( 100 g , 0 . 829 mol ), aniline ( 2 . 09 g , 2 . 25 mol ) and potassium iodide ( 1 . 0 g ) was heated at 130 ° c . under nitrogen for 36 hours and cooled to room temperature . a 3n hydrochloric acid solution ( 400 ml ) was added and the solution was washed several times with isopropyl ether and made basic with a 50 % sodium hydroxide solution . the product was extracted three times into isopropyl ether , washed twice with water and once with a saturated sodium chloride solution , dried ( sodium sulfate ), filtered and evaporated to a liquid that was added to water ( 3l ) and extracted into three portions of isopropyl ether . the combined extracts were washed twice with water and once with a saturated sodium chloride solution , dried ( magnesium sulfate ), treated with charcoal , filtered and evaporated under reduced pressure to a liquid ( 91 . 4 g ). a 6 . 0 g portion was dissolved in isopropanol and a solution of oxalic acid ( 3 . 1 g ) in isopropanol was added . the resulting solid was collected by filtration and rinsed with isopropyl ether to give 6 . 3 g of solid . a 1 . 5 g portion was recrystallized from isopropanol / isopropyl ether / light pet ether to give a solid that was removed by filtration . a second crop of crystals was obtained from the filtrate , dried under high vacuum at 60 ° c . to give 0 . 31 g , mp 149 °- 156 ° c . analysis : calculated for c 13 h 17 no 5 : c , 58 . 42 ; h , 6 . 41 ; n , 5 . 24 ; found : c , 57 . 99 ; h , 6 . 41 ; n , 5 . 37 . a solution of phosgene ( 287 ml of a 20 % solution , 273 g , 0 . 55 mol ) in toluene and additional toluene ( 100 ml ) was cooled to - 10 ° c . by an ice / methanol bath and a solution of tetrahydro - n -( 1 - methylethyl )- 2h - pyran - 2 - methanamine ( 41 . 13 g , 0 . 262 mol ) and triethylamine ( 27 . 9 g , 0 . 276 mol ) in toluene ( 300 ml ) was added dropwise , keeping the temperature below 5 ° c . the mixture was warmed to room temperature and refluxed under nitrogen for 30 min . zinc chloride ( 0 . 65 g ) was added and refluxing was continued for 15 min . an additional portion of zinc chloride ( 0 . 32 g ) was added , and the mixture was refluxed for 24 hr and allowed to stand at room temperature for several days . water ( 750 ml ) was added , and the layers were separated . the organic layer was washed twice again with water and once with a saturated sodium chloride solution , dried ( magnesium sulfate ), treated with charcoal , filtered , and evaporated to an oil . the oil was distilled under reduced pressure , and the fraction distilling from 148 °- 165 ° c ./ 0 . 3 mm was collected to give 46 . 7 g ( 81 % yield ). analysis : calculated for c 10 h 18 no 2 cl : c , 54 . 67 ; h , 8 . 26 ; n , 6 . 38 ; found : c , 53 . 37 ; h , 8 . 37 ; n , 6 . 15 . to a solution of phosgene in toluene ( 342 g of a 20 % solution , 0 . 693 mol ) was added additional toluene ( 150 ml ) and the solution was cooled to - 10 ° c . in an ice / methanol bath . dropwise , keeping the temperature below 5 ° c ., a solution of 2 - phenylaminomethyltetrahydrofuran ( 58 . 4 g , 0 . 330 mol ) and triethylamine ( 35 . 1 g , 0 . 348 mol ) in toluene ( 400 ml ) was added . the mixture was warmed to room temperature and then refluxed for 30 minutes . zinc chloride ( 0 . 82 g ) was added and refluxing was continued for 15 minutes . an additional portion of zinc chloride ( 0 . 41 g ) was added and the mixture was refluxed under nitrogen for 24 hours . the mixture was washed twice with water , once with a saturated sodium chloride solution , dried ( sodium sulfate ), filtered , and evaporated under reduced pressure to an oil , which crystallized upon standing ( 70 . 7 g , 89 % yield ). recrystallization from isopropanol / isopropyl ether gave 47 . 0 g of solid , from which a 1 . 5 g portion was again recrystallized from isopropanol / isopropyl ether and dried under high vacuum to give 1 . 18 g , mp 76 °- 79 ° c . analysis : calculated for c 12 h 14 no 2 cl : c , 60 . 13 ; h , 5 . 89 ; n , 5 . 84 ; found : c , 60 . 11 ; h , 5 . 97 ; n , 5 . 81 . to a 20 % solution of phosgene in toluene ( 273 g of solution , 0 . 55 mol ) was added toluene ( 100 ml ) and the solution was stirred in an ice / methanol bath . a solution of 2 - phenylaminomethyltetrahydropyran ( 50 . 0 g , 0 . 262 mol ) and triethylamine ( 27 . 9 g , 0 . 276 mol ) in toluene ( 300 ml ) was added dropwise , keeping the temperature below 5 ° c . the mixture was warmed to room temperature and then refluxed for 30 minutes . zinc chloride ( 0 . 65 g ) was added and the mixture was refluxed for 15 minutes . an additional portion of zinc chloride ( 0 . 32 g ) was added and the mixture was refluxed for 10 minutes and stirred at room temperature for 3 days . the mixture was again refluxed for 24 hours , cooled to room temperature , washed twice with water , and twice with a saturated sodium chloride solution , dried ( magnesium sulfate ), treated with charcoal , filtered , and evaporated under reduced pressure to give 57 . 8 g ( 87 % yield ) of solid , which was recrystallized from isopropanol / isopropyl ether to give 38 . 0 g of product . a 1 . 5 g portion was gain recrystallized from isopropanol / isopropyl ether and dried under high vacuum to give 0 . 92 g , mp 65 °- 69 ° c . analysis : calculated for c 13 h 16 no 2 cl : c , 61 . 54 ; h , 6 . 36 ; n , 5 . 52 ; found : c , 61 . 50 ; h , 6 . 44 ; n , 5 . 50 . a mixture of 5 -( 4 - chlorobutyl )- 3 - methyl - 2 - oxazolidinone ( 10 . 0 g , 0 . 0524 mol ), 1 - phenylpiperazine hydrochloride ( 0 . 0524 mol , 10 . 39 g ), potassium carbonate ( 28 . 94 g , 0 . 209 mol ) and potassium iodide ( 1 . 0 g ) was refluxed in 1 - butanol ( 150 ml ) for 24 hr and then stirred at room temperature for two days . the mixture was reheated to boiling and filtered hot . methanolic hydrogen chloride was added to acidify the filtrate and addition of isopropyl ether caused a solid to precipitate . the solid was collected by filtration and dissolved in water . potassium carbonate was added to make the solution basic and the product was extracted into two portions of ethyl acetate . the combined ethyl acetate layers were washed twice with water , three times with a saturated sodium bicarbonate solution and once with a saturated sodium chloride solution . the solution was dried ( sodium sulfate ), filtered , and evaporated under reduced pressure to an oil . addition of isopropyl ether gave a solid which was recrystallized from isopropyl ether / methanol . the solid was collected by filtration , rinsed with light pet ether and dried under high vacuum to give 7 . 51 g ( 45 % yield ), mp 85 °- 88 ° c . analysis : calculated for c 18 h 27 n 3 o 2 : c , 68 . 11 ; h , 8 . 57 ; n , 13 . 24 ; found : c , 68 . 10 ; h , 8 . 68 ; n , 13 . 28 . following the procedure of example 1 , the title compound is prepared from a mixture of 5 -( 4 - chlorobutyl )- 3 - methyl - 2 - oxazolidinone ( 5 . 0 g , 0 . 0262 mol ), 1 -( 2 - pyridinyl ) piperazine ( 4 . 56 g , 0 . 0279 mol ) and potassium carbonate ( 8 . 5 g , 0 . 0614 mol ) in 1 - butanol ( 50 ml ) to obtain 3 . 4 g ( 41 % yield ) of solid . recrystallization from ethyl acetate / petroleum ether followed by drying in vacuo gave 1 . 46 g of the title compound , mp 69 °- 72 ° c . analysis : calculated for c 17 h 26 n 4 o 2 : c , 64 . 12 ; h , 8 . 23 ; n , 17 . 60 ; found : c , 64 . 01 ; h , 8 . 29 ; n , 17 . 58 . following the procedures of example 1 , the title compound is prepared . thus , a mixture of 5 -( 4 - chlorobutyl )- 3 - methyl - 2 - oxazolidinone ( 5 . 0 g , 0 . 0262 mol ), 1 -( 2 - methoxyphenyl ) piperazine ( 5 . 4 g . 0 . 0279 mol ), potassium carbonate ( 8 . 5 g , 0 . 0614 mol ), and potassium iodide ( 0 . 75 g ) in 1 - butanol ( 50 ml ) gave 6 . 8 g of oil which was dissolved in hot methanol and acidified with methanolic hydrogen chloride . addition of isopropyl ether and isopropanol to the cloud point and cooling gave a solid which was collected by filtration , rinsed with isopropyl ether and light pet ether and dried under high vacuum to give 4 . 22 g ( 38 % yield ), mp 209 °- 216 ° c . analysis : calculated for c 19 h 29 n 3 o 3 . 2hcl : c , 54 . 28 ; h , 7 . 43 ; n , 10 . 00 ; found : c , 54 . 16 ; h , 7 . 72 ; n , 9 . 98 . following the procedure of example 1 , mixture of 5 -( 4 - chlorobutyl )- 3 - methyl - 2 - oxazolidinone ( 5 . 0 g , 0 . 0262 mol ), 1 -( 2 - pyrimidinyl ) piperazine dihydrochloride ( 6 . 62 g , 0 . 0279 mol ), potassium carbonate ( 19 . 3 g , 0 . 140 mol ) and potassium iodide ( 0 . 75 g ) in 1 - butanol ( 75 ml ) gave an oil ( 3 . 0 g ) which crystallized upon standing . recrystallization from ethyl acetate / light pet ether followed by drying under high vacuum gave 1 . 33 g ( 16 % yield ), mp 74 °- 76 ° c . analysis : calculated for c 16 h 25 n 5 o 2 : c , 60 . 17 ; h , 7 . 89 ; n , 21 . 92 ; found : c , 60 . 02 ; h , 8 . 02 ; n , 21 . 96 . a mixture of 5 -( 3 - chloropropyl )- 3 - methyl - 2 - oxazolidinone ( 5 . 0 g , 0 . 0282 mol ), 1 -( 2 - methoxyphenyl ) piperazine ( 5 . 43 g , 0 . 0282 mol ), potassium carbonate ( 11 . 71 g , 0 . 0847 mol ), and potassium iodide ( 0 . 5 g ) in 1 - butanol ( 75 ml ) was refluxed for 24 hours under nitrogen and filtered hot . a 3n hydrochloride acid solution was added to acidify the filtrate , and the aqueous solution was washed twice with isopropyl ether . the aqueous solution was made basic with potassium carbonate , and the product was extracted into two portions of ethyl acetate . the combined ethyl acetate layers were washed three times with water and once with a saturated sodium chloride solution , dried ( sodium sulfate ), filtered , and evaporated under reduced pressure to an oil ( 7 . 1 g , 76 % yield ). the oil was dissolved in hot isopropanol , acidified with ethereal hydrogen chloride , and allowed to cool . the resulting solid was collected by filtration , rinsed with diethyl ether , and dried under high vacuum at 60 ° to give 6 . 92 g , mp 199 °- 202 ° c . analysis : calc . for c 18 h 27 n 3 o 3 . hcl . 1 . 5h 2 o : c , 54 . 47 ; h , 7 . 87 ; n , 10 . 59 ; found : c , 54 . 23 ; h , 7 . 53 ; n , 10 . 50 . following the procedure of example 5 , a mixture of 5 -( 3 - chloropropyl )- 3 - methyl - 2 - oxazolidinone ( 5 . 0 g , 0 . 0282 mol ), 1 -( 2 - pyridinyl ) piperazine ( 4 . 61 g , 0 . 0282 mol ), potassium carbonate ( 11 . 71 g , 0 . 0847 mol ), and potassium iodide ( 0 . 5 g ) in 1 - butanol ( 75 ml ) gave an oil ( 4 . 2 g , 49 % yield ). the oil was dissolved in hot isopropanol and acidified with ethereal hydrogen chloride . methanol was added to make a solution . upon cooling , a solid precipitated which was collected by filtration , rinsed with diethyl ether , and dried under high vacuum at 60 ° c . to give 3 . 66 g , mp 214 °- 218 ° c . analysis : calc . for c 16 h 24 n 4 o 2 . 2hcl . 0 . 5h 2 o : c , 49 . 74 ; h , 7 . 04 ; n , 14 . 50 ; found : c , 49 . 73 ; h , 7 . 22 ; n , 14 . 51 . following the procedure of examples 5 , 5 -( 3 - chloropropyl )- 3 - methyl - 2 - oxazolidinone ( 5 . 0 g , 0 . 0282 mol ), 1 -( 2 - pyrimidinyl ) piperazine dihydrochloride ( 6 . 70 g , 0 . 0282 mol ), potassium carbonate ( 23 . 4 g , 0 . 1695 mol ), and potassium iodide ( 0 . 5 g ) in 1 - butanol ( 100 ml ) gave an oil ( 3 . 5 g , 41 % yield ) which was dissolved in a hot mixture of isopropyl ether and isopropanol , filtered hot , and brought to the cloud point by the addition of light pet ether . upon cooling , a solid precipitated which was collected by filtration , rinsed with light pet ether , and dried under high vacuum to give 1 . 38 g , mp 79 °- 89 ° c . analysis : calculated for c 15 h 23 n 5 o 2 : c , 59 . 00 ; h , 7 . 59 ; n , 22 . 93 ; found : c , 58 . 96 ; h , 7 . 75 ; n , 22 . 91 . following the procedure of example 5 , a mixture of 5 -( 3 - chloropropyl )- 3 - methyl - 2 - oxazolidinone ( 5 . 0 g , 0 . 0282 mol ), 1 -( 2 - ethoxyphenyl ) piperazine monohydrochloride ( 6 . 86 g , 0 . 0282 mol ), potassium carbonate ( 15 . 62 g , 0 . 113 mol ), and potassium iodide ( 1 . 0 g ) in n - butanol ( 100 ml ) gave an oil ( 4 . 5 g , 46 % yield ). the oil was triturated in warm isopropyl ether and the resulting suspension was stirred at room temperature . the solid was collected by filtration , rinsed with light pet ether and dried under high vacuum to give 2 . 58 g , mp 79 °- 81 ° c . analysis : calculated for c 19 h 29 n 3 o 3 : c , 65 . 68 ; h , 8 . 41 ; n , 12 . 09 ; found : c , 65 . 80 ; h , 8 . 55 ; n , 12 . 07 . following the procedure of example 5 , a mixture of 5 -( 2 - chlorobutyl )- 3 - methyl - 2 - oxazolidinone ( 5 . 2 g , 0 . 0272 mol ), 1 -( 2 - ethoxyphenyl ) piperazine monohydrochloride ( 6 . 61 g , 0 . 0272 mol ), potassium carbonate ( 15 . 05 g , 0 . 109 mol ), and potassium iodide ( 1 . 0 g ) in n - butanol ( 100 ml ) gave an oil which was dissolved in a mixture of ethyl acetate / isopropyl ether / light pet ether ( removing the impurities by filtration ) and acidified with ethereal hydrogen chloride . the mixture was evaporated under reduced pressure and recrystallized once from isopropanol / methanol / isopropyl ether and then from isopropanol / isopropyl ether and dried under high vacuum at 60 ° c . to give 1 . 18 g ( 10 % yield ), mp 207 °- 212 ° c . analysis : calculated for c 20 h 31 n 3 o 3 . 2hcl : c , 55 . 30 ; h , 7 . 66 ; n , 9 . 67 ; found : c , 55 . 14 ; h , 7 . 79 ; n , 9 . 61 . following the procedure of example 5 , a mixture of 1 -( 2 - hydroxyphenyl ) piperazine dihydrobromide ( 9 . 6 g , 0 . 0282 mol ), 5 -( 3 - chloropropyl )- 3 - methyl - 2 - oxazolidinone ( 5 . 0 g , 0 . 0282 mol ), sodium bicarbonate ( 9 . 5 g , 0 . 113 mol ), and potassium iodide in 1 - butanol ( 100 ml ) gave an oil . the oil was triturated several times with light pet ether ( decanting each time ) and dissolved in ethyl acetate / isopropyl ether . cooling the solution gave a solid which was collected by filtration and dried under high vacuum to give 1 . 80 g ( 20 % yield ), mp 112 °- 116 ° c . analysis : calculated for c 17 h 25 n 3 o 3 : c , 63 . 93 ; h , 7 . 89 ; n , 13 . 16 ; found : c , 63 . 71 ; h , 8 . 01 ; n , 13 . 04 . following the procedure of example 5 , a mixture of 5 -( 4 - chlorobutyl )- 3 - methyl - 2 - oxazolidinone ( 5 . 39 g , 0 . 0282 mol ), 1 -( 2 - hydroxyphenyl )- piperazine dihydrobromide ( 9 . 6 g , 0 . 0282 mol ), sodium bicarbonate ( 9 . 5 g , 0 . 113 mol ) and potassium iodide ( 1 . 0 g ) in n - butanol ( 100 ml ) gave an oil which was triturated in light pet ether several times , crystallized from ethyl acetate / isopropyl ether , and dried under high vacuum at 50 ° c . to give 3 . 22 g ( 34 % yield ), mp 106 °- 110 °. analysis : calculated for c 18 h 27 n 3 o 3 : c , 64 . 84 ; h , 8 . 16 ; n , 12 . 60 ; found : c , 64 . 79 ; h , 8 . 36 ; n , 12 . 54 . to a stirring solution of 5 -[ 4 -[ 4 ( 2 - hydroxyphenyl )- 1 - piperazinyl ] butyl - 3 - methyl - 2 - oxazolidinone ( 5 . 0 g , 0 . 0150 mol ) in absolute ethanol ( 150 ml ) was added a solution of potassium hydroxide ( 0 . 93 g , 0 . 0165 mol ) in absolute ethanol ( 100 ml ). the mixture was stirred at room temperature for 30 minutes and allyl bromide ( 2 . 00 g , 0 . 0165 mol ) was added . the mixture was stirred at room temperature for 3 hr and acidified with a 3n hydrochloric acid solution . the solvents were removed under reduced pressure and a saturated sodium bicarbonate solution and ethyl acetate were added . the layers were separated and the aqueous layer was extracted again with ethyl acetate . the combined organic layers were washed twice with a saturated sodium chloride solution , twice with a 5 % potassium hydroxide solution , once more with a saturated sodium chloride solution , dried ( sodium sulfate ), filtered , and evaporated under reduced pressure to 3 . 7 g of a liquid , which was dissolved in absolute ethanol and acidified with ethanolic hydrogen chloride . the solid was collected by filtration , rinsed with diethyl ether and dried under high vacuum at 60 ° c ., giving 3 . 15 g ( 46 % yield ), mp 197 °- 200 ° c . analysis : calc . for c 21 h 31 n 3 o 3 . 2hcl . 0 . 5h 2 o : c , 55 . 38 ; h , 7 . 52 ; n , 9 . 23 ; found : c , 55 . 93 ; h , 7 . 62 ; n , 9 . 36 . following the procedure of example 5 , a mixture of 5 -( 4 - chlorobutyl )- 3 - phenyl - 2 - oxazolidinone ( 3 . 0 g , 0 . 01186 mol ), 1 ( 2methyoxyphenyl )- piperazine ( 2288g , 0 . 01186 mol ), potassium carbonate ( 4 . 92 g , 0 . 0356 mol ) and potassium iodide ( 1 g ) in 1 - butanol ( 75 ml ) gave an oil ( 4 . 7 g , 87 % yield ), which was crystallized from isopropanol / isopropyl ether . drying of the resulting solid under high vacuum gave 0 . 98 g , mp 153 °- 155 ° c . analysis : calc . for c 24 h 31 n 3 o 3 . hcl . 0 . 5h 2 o : c , 63 . 36 ; h , 7 . 31 ; n , 9 . 24 ; found : c , 63 . 60 ; h , 7 . 33 ; n , 9 . 12 . following the procedure of example 5 , a mixture of 5 -( 4 - chlorobutyl )- 3 - phenyl - 2 - oxazolidinone ( 3 . 0 g , 0 . 01186 mol ), 1 -( 2 - pyridinyl ) piperazine ( 1 . 94 g , 0 . 01186 mol ), potassium carbonate ( 4 . 92 g , 0 . 0356 mol ), and potassium iodide ( 1 . 0 g ) in n - butanol ( 75 ml ) gave an oil , which crystallized upon standing ( 3 . 9 g , 86 % yield ). the solid was recrystallized from isopropanol / isopropyl ether and dried under high vacuum to give 1 . 80 g , mp 78 °- 81 ° c . analysis : calculated for c 22 h 28 n 4 o 2 : c , 69 . 45 ; h , 7 . 42 ; n , 14 . 72 ; found : c , 69 . 33 ; h , 7 . 51 ; n , 14 . 56 . following the procedure of example 5 , a mixture of 5 -( 4 - chlorobutyl )- 3 - phenyl - 2 - oxazolidinone ( 3 . 0 g , 0 . 01186 mol ), 1 -( 2 - pyrimidinyl ) piperazine dihydrochloride ( 2 . 81 g , 0 . 01186 mol ), potassium carbonate ( 9 . 85 g , 0 . 0713 mol ), and potassium iodide ( 1 . 0 g ) in n - butanol ( 75 ml ) gave a solid ( 4 . 1 g , 91 % yield ). the solid was recrystallized from isopropanol / isopropyl ether and dried under high vacuum to give 2 . 58 g , mp 94 °- 96 ° c . analysis : calculated for c 21 h 27 n 5 o 2 : c , 66 . 12 ; h , 7 . 13 ; n , 18 . 36 ; found : c , 66 . 04 ; h , 7 . 17 ; n , 18 . 29 . following the procedure of example 5 , a mixture of 5 -( 4 - chlorobutyl )- 3 - phenyl - 2 - oxazolidinone ( 3 . 0 g , 0 . 01186 mol ), 1 - phenylpiperazine hydrochloride ( 2 . 35 g , 0 . 01186 mol ), potassium carbonate ( 6 . 54 g , 0 . 0473 mol ), and potassium iodide ( 1 . 0 g ) in 1 - butanol gave a liquid ( 4 . 1 g , 91 % yield ) which crystallized upon standing . recrystallization from isopropanol / isopropyl /- ether and drying under high vacuum gave 1 . 44 g , mp 83 °- 85 ° c . analysis : calculated for c 23 h 29 n 3 o 2 : c , 72 . 79 ; h , 7 . 70 ; n , 11 . 07 ; found : c , 72 . 76 ; h , 7 . 90 ; n , 10 . 86 . following the procedure of example 5 , a mixture of 5 -( 4 - chlorobutyl )- 3 - phenyl - 2 - oxazolidinone ( 6 . 0 g , 0 . 0237 mol ), 1 -( 2 - hydroxyphenyl ) piperazine dihydrobromide ( 8 . 06 g , 0 . 0237 mol ), sodium bicarbonate ( 7 . 98 g , 0 . 095 mol ), and potassium iodide ( 1 . 0 g ) in n - butanol ( 200 ml ) gave an oil ( 10 . 5 g ) which crystallized on standing and was recrystallized from isopropanol / isopropyl ether . drying under high vacuum gave 6 . 15 g ( 66 % yield ), mp 123 °- 129 ° c . analysis : calculated for c 23 h 29 n 3 o 3 : c , 69 . 85 ; h , 7 . 39 ; n , 10 . 62 ; found : c , 69 . 72 ; h , 7 . 52 ; n , 10 . 44 . following the procedure of example 5 , a mixture of 5 -( 4 - chlorobutyl )- 3 - phenyl - 2 - oxazolidinone , ( 3 . 0 g , 0 . 01186 mol ), 1 -( 2 - ethoxyphenyl ) piperazine hydrochloride ( 2 . 88 g , 0 . 01186 mol ), potassium carbonate ( 6 . 57 g , 0 . 0475 mol ), and potassium iodide ( 1 . 0 g ) in n - butanol ( 100 ml ) gave an oil ( 3 . 5 g , 79 % yield ). the oil was dissolved in ethanolic hydrogen chloride and allowed to stand . diethyl ether was added to give a solid which was collected by filtration . after recrystallization the solid weighted 3 . 64 g , mp 215 °- 223 ° c . analysis : calc . for c 26 h 33 n 3 o 3 . 2hcl . 0 . 5h 2 o : c , 59 . 40 ; h , 7 . 18 ; n , 8 . 31 ; found : c , 59 . 24 ; h , 7 . 22 ; n , 8 . 44 . following the procedure of example 5 , a mixture of 5 -( 3 - chloropropyl )- 3 - phenyl - 2 - oxazolidinone ( 4 . 5 g , 0 . 0188 mol ), 1 -( 2 - pyridinyl ) piperazine ( 3 . 07 g , 0 . 0188 mol ), potassium carbonate ( 7 . 81 g , 0 . 0565 mol ), and potassium iodide ( 1 . 0 g ) in n - butanol ( 200 ml ) gave a solid which was recrystallized from isopropanol / isopropyl ether and dried under high vacuum to give 3 . 86 g ( 56 % yield ), mp 123 °- 125 ° c . analysis : calculated for c 21 h 26 n 4 o 2 : c , 68 . 83 ; h , 7 . 15 ; n , 15 . 29 ; found : c , 68 . 70 ; h , 7 . 16 ; n , 15 . 22 . following the procedure of example 5 , a mixture of 5 -( 3 - chloropropyl )- 3 - phenyl - 2 - oxazolidinone ( 4 . 5 g , 0 . 0188 mol ), 1 -( 2 - pyrimidyl ) piperazine dihydrochloride ( 4 . 47 g , 0 . 0188 mol ), potassium carbonate ( 15 . 64 g , 0 . 113 mol ), and potassium iodide ( 1 . 0 g ) in n - butanol ( 200 ml ) gave a solid which was recrystallized from isopropanol / isopropyl ether and dried under high vacuum to give 2 . 49 g ( 36 % yield ), mp 92 °- 98 ° c . and 118 ° c . analysis : calculated for c 20 h 25 n 5 o 2 : c , 65 . 37 ; h , 6 . 86 ; n , 19 . 05 ; found : c , 65 . 27 ; h , 6 . 85 ; n , 19 . 01 . following the procedure of example 5 , a mixture of 5 -( 3 - chloropropyl )- 3 - phenyl - 2 - oxazolidinone ( 4 . 5 g , 0 . 0188 mol ), 1 -( 2 - ethoxyphenyl ) piperazine hydrochloride ( 4 . 57 g , 0 . 0188 mol ), potassium carbonate ( 10 . 42 , g 0 . 0754 mol ), and potassium iodide ( 1 . 0 g ) in n - butanol ( 200 ml ) gave an oil . acidification with ethanolic hydrogen chloride followed by addition of diethyl ether gave a solid , which was collected by filtration and dried under high vacuum to give 3 . 97 g ( 43 % yield ), mp 182 °- 187 ° c . analysis : calculated for c 24 h 31 n 3 o 3 . hcl . 0 . 5h 2 o : c , 58 . 66 ; h , 6 . 97 ; n , 8 . 55 ; found : c , 58 . 63 ; h , 7 . 10 ; n . 8 . 30 . following the procedure of example 5 , a mixture of 5 -( 3 - chloropropyl )- 3 - phenyl - 2 - oxazolidinone ( 4 . 5 g , 0 . 0188 mol ), 1 - phenylpiperazine hydrochloride ( 3 . 74 g , 0 . 0188 mol ), potassium carbonate ( 10 . 38 g , 0 . 0751 mol ), and potassium iodide ( 1 . 0 g ) in n - butanol ( 200 ml ) gave a solid ( 6 . 2 g , 90 % yield ), recrystallization from isopropanol / isopropyl ether and drying under high vacuum gave 2 . 60 g , mp 125 °- 127 ° c . analysis : calculated for c 22 h 27 n 3 o 2 : c , 72 . 30 ; h , 74 . 5 ; n , 11 . 50 ; found : c , 72 . 05 ; h , 7 . 48 ; n , 11 . 40 . following the procedure of example 5 , a mixture of 5 -( 3 - chloropropyl )- 3 - phenyl - 2 - oxazolidinone ( 4 . 5 g , 0 . 0188 mol ), 1 -( 2 - methoxyphenyl )- piperazine ( 3 . 62 g , 0 . 0188 mol ), potassium carbonate ( 7 . 81 g , 0 . 0565 mol ), and potassium iodide ( 1 . 0 g ) in n - butanol ( 200 ml ) gave an oil . the oil was acidified with warm ethanolic hydrogen chloride , filtered warm , and cooled to room temperature . diethyl ether was added and the resulting solid was collected by filtration and dried under high vacuum at 50 ° c . to give 4 . 65 g ( 53 % yield ), mp 203 °- 211 ° c . analysis : calculated for c 23 h 29 n 3 o 3 . 2hcl : c , 58 . 98 ; h , 6 . 67 ; n , 8 . 97 ; found : c , 59 . 02 ; h , 6 . 89 ; n , 8 . 93 . following the procedure of example 5 , a mixture of 5 -( 3 - chloropropyl )- 3 - phenyl - 2 - oxazolidinone ( 9 . 0 g , 0 . 0376 mol ), 1 -( 2 - hydroxyphenyl ) piperazine dihydrobromide ( 12 . 80 g , 0 . 0377 mol ), sodium bicarbonate ( 12 . 66 g , 0 . 151 mol ), and potassium iodide ( 1 . 0 g ) in n - butanol ( 400 ml ) gave an oil ( 9 . 3 g , 65 % yield ). the oil was dissolved in warm absolute ethanol and acidified with ethanolic hydrogen chloride . ether was added and the solid was collected by filtration and dried under high vacuum at 60 ° c . to give 8 . 28 g , mp 250 ° c . analysis : calculated for c 22 h 27 n 3 o 2 . 2hcl : c , 58 . 15 ; h , 6 . 43 ; n , 9 . 25 ; found : c , 58 . 00 ; h , 6 . 51 ; n , 9 . 20 . a mixture of 5 -[ 4 -[ 4 -( 2 - hydroxyphenyl )- 1 - piperazinyl ] butyl ]- 3 - phenyl - 2 - oxazolidinone ( 4 . 0 g , 0 . 0101 mol ) and potassium hydroxide ( 0 . 62 g , 0 . 011 mol ) in absolute ethanol ( 250 ml ) was stirred at room temperature for two hours and allyl bromide ( 1 . 34 g , 0 . 0111 mol ) was added . the mixture was stirred at room temperature for 4 days and then acidified with a 3n hydrochloric acid solution . the solvents were removed under reduced pressure and then the residue was dissolved in a saturated sodium bicarbonate solution . the product was extracted twice into ethyl acetate , washed once with water , twice with a 5 % potassium hydroxide solution , once again with water and once with a saturated sodium chloride solution , dried ( sodium sulfate ), filtered and evaporated under reduced pressure to an oil ( 4 . 3 g , 98 % yield ). the oil was dissolved in warm absolute ethanol and acidified with ethanolic hydrogen chloride . the resulting solid was collected by filtration , rinsed with ether and dried under high vacuum at 50 ° c . to give 3 . 5 g , mp 198 °- 202 ° c . analysis : calculated for c 26 h 33 n 3 o 3 . 2hcl : c , 61 . 41 ; h , 6 . 94 ; n , 8 . 26 ; found : c , 60 . 98 ; h , 7 . 12 ; n , 8 . 18 . a mixture of 5 -[ 3 -[ 4 -( 2 - hydroxyphenyl )- 1 - piperazinyl ] propyl ]- 3 - phenyl - 2 - oxazolidinone dihydrochloride ( 4 . 0 g , 0 . 0101 mol ) and potassium hydroxide ( 0 . 62 g , 0 . 0111 mol ) in absolute ethanol ( 250 ml ) was stirred at room temperature for two hours and allyl bromide ( 1 . 34 g , 0 . 0111 mol ) was added . the mixture was stirred at room temperature for 4 days and then acidified with a 3n hydrochloric acid solution . the solvents were removed under reduced pressure and a saturated sodium bicarbonate solution was added to the residue . the product was extracted twice into ethyl acetate and the combined extracts were washed once with water , twice with a 5 % potassium hydroxide solution , once again with water and once with a saturated sodium chloride solution , dried ( sodium sulfate ), filtered and evaporated under reduced pressure to an oil ( 4 . 3 g , 98 % yield ). the oil was dissolved in warm absolute ethanol and acidified with ethanolic hydrogen chloride . the resulting solid was collected by filtration , rinsed with ether and dried under high vacuum at 50 ° c . to give 3 . 5 g , mp 198 °- 202 ° c . analysis : calculated for c 25 h 31 n 3 o 3 . hcl . 1 . 5h 2 o : c , 61 . 91 ; h , 7 . 27 ; n , 8 . 66 ; found : c , 62 . 19 ; h , 6 . 91 ; n , 8 . 84 . following the procedure of example 5 , a mixture of 5 -( 4 - chlorobutyl )- 3 -( 1 - methylethyl )- 2 - oxazolidinone ( 5 . 2 g , 0 . 0237 mol ), 1 -( 2 - methoxyphenyl ) piperazine ( 4 . 56 g , 0 . 0237 mol ), potassium carbonate ( 9 . 84 g , 0 . 0712 mol ) and potassium iodide ( 1 . 0 g ) in n - butanol ( 200 ml ) gave an oil . the oil was dissolved in absolute ethanol and acidified with ethanolic hydrogen chloride . addition of ether gave a solid which was collected by filtration and dried under high vacuum at 70 ° c . to give 7 . 36 g ( 69 % yield ), mp 206 °- 213 ° c . analysis : calculated for c 21 h 33 n 3 o 3 . 2hcl : c , 56 . 25 ; h , 7 . 87 ; n , 9 . 37 ; found : c , 56 . 18 ; h , 8 . 13 ; n , 9 . 31 . following the procedure of example 5 , a mixture of 5 -( 4 - chlorobutyl )- 3 -( 1 - methylethyl )- 2 - oxazolidinone ( 5 . 2 g , 0 . 0137 mol ), 1 -( 2 - ethoxyphenyl )- piperazine hydrochloride ( 5 . 76 g , 0 . 0237 mol ) and potassium iodide ( 1 . 0 g ) in n - butanol ( 200 ml ) gave an oil . the oil was dissolved in absolute ethanol and acidified with ethanolic hydrogen chloride . addition of ether and filtration gave a solid which was dried under high vacuum at 70 ° c . to give 6 . 62 g ( 60 % yield ), mp 199 °- 205 ° c . analysis : calculated for c 22 h 35 n 3 o 3 . 2hcl : c , 57 . 14 ; h , 8 . 06 ; n , 9 . 09 ; found : c , 57 . 25 ; h , 8 . 42 ; n , 9 . 07 . following the procedure of example 5 , a mixture of 5 -( 4 - chlorobutyl )- 3 -( 1 - methylethyl )- 2 - oxazolidinone ( 10 . 4 g , 0 . 0474 mol ), 1 -( 2 - hydroxyphenyl ) piperazine dihydrobromide ( 16 . 12 g , 0 . 0474 mol ), sodium bicarbonate ( 15 . 96 g , 0 . 190 mol ) and potassium iodide ( 1 . 0 ) in n - butanol ( 350 ml ) gave an oil . the oil was dissolved in absolute ethanol and acidified with ethanolic hydrogen chloride . addition of ether and filtration gave a solid which was dried under high vacuum at 70 ° c . to give 9 . 47 g ( 46 % yield ), mp 203 °- 207 ° c . analysis : calculated for c 20 h 31 n 3 o 3 . 2hcl : c , 55 . 30 ; h , 7 . 66 ; n , 9 . 67 ; found : c , 54 . 97 ; h , 7 . 97 ; n , 9 . 49 . table i______________________________________formula i examples ## str11 ## examples ar n r______________________________________ 1 c . sub . 6 h . sub . 5 4 ch . sub . 3 2 2 - pyridinyl 4 ch . sub . 3 3 2 - ch . sub . 3 oc . sub . 6 h . sub . 4 4 ch . sub . 3 4 2 - pyrimidinyl 4 ch . sub . 3 5 2 - ch . sub . 3 oc . sub . 6 h . sub . 4 3 ch . sub . 3 6 2 - pyridinyl 3 ch . sub . 3 7 2 - pyrimidinyl 3 ch . sub . 3 8 2 - c . sub . 2 h . sub . 5 oc . sub . 6 h . sub . 4 3 ch . sub . 3 9 2 - c . sub . 2 h . sub . 5 oc . sub . 6 h . sub . 4 4 ch . sub . 310 2 - hoc . sub . 6 h . sub . 4 3 ch . sub . 311 2 - hoc . sub . 6 h . sub . 4 4 ch . sub . 312 2 -( ch . sub . 2chch . sub . 2 o ) c . sub . 6 h . sub . 4 4 ch . sub . 313 2 - ch . sub . 3 oc . sub . 6 h . sub . 4 4 c . sub . 6 h . sub . 514 2 - pyridinyl 4 c . sub . 6 h . sub . 515 2 - pyrimidinyl 4 c . sub . 6 h . sub . 516 c . sub . 6 h . sub . 5 4 c . sub . 6 h . sub . 517 2 - hoc . sub . 6 h . sub . 4 4 c . sub . 6 h . sub . 518 2 - c . sub . 2 h . sub . 5 oc . sub . 6 h . sub . 4 4 c . sub . 6 h . sub . 519 2 - pyridinyl 3 c . sub . 6 h . sub . 520 2 - pyrimidinyl 3 c . sub . 6 h . sub . 521 2 - c . sub . 2 h . sub . 5 oc . sub . 6 h . sub . 4 3 c . sub . 6 h . sub . 522 c . sub . 6 h . sub . 5 3 c . sub . 6 h . sub . 523 2 - ch . sub . 3 oc . sub . 6 h . sub . 4 3 c . sub . 6 h . sub . 524 2 - hoc . sub . 6 h . sub . 4 3 c . sub . 6 h . sub . 525 2 -( ch . sub . 2chch . sub . 2 o ) c . sub . 6 h . sub . 4 4 c . sub . 6 h . sub . 526 2 -( ch . sub . 2chch . sub . 2 o ) c . sub . 6 h . sub . 4 3 c . sub . 6 h . sub . 527 2 - ch . sub . 3 oc . sub . 6 h . sub . 4 4 ch ( ch . sub . 3 ). sub . 228 2 - c . sub . 2 h . sub . 5 oc . sub . 6 h . sub . 4 4 ch ( ch . sub . 3 ). sub . 229 2 - hoc . sub . 6 h . sub . 4 4 ch ( ch . sub . 3 ). sub . 2______________________________________ anxiolytic test data obtained ( competitive binding to 5ht 1a receptors or expiratory light / dark behavior ) for the invention compounds and a reference compound are shown in table ii . table ii______________________________________pharmacology dataex - light / ample 5ht . sub . 1a . sup . 1 dark . sup . 2 example 5ht . sub . 1a light / dark . sup . 2______________________________________1 59 56 ( 10 ) 16 8 . 2 -- 2 61 53 ( 3 . 16 ) 17 15 -- 3 15 53 ( 3 . 16 ) 18 2 . 0 -- 4 190 -- 19 57 -- 5 29 -- 20 170 -- 6 110 -- 21 18 -- 7 510 -- 22 50 -- 8 22 -- 23 11 -- 9 16 -- 24 -- -- 10 110 -- 25 -- -- 11 40 -- 26 -- -- 12 20 66 ( 1 ) 27 -- -- 13 2 . 2 -- 28 -- -- 14 7 . 7 -- 29 -- -- 15 29 -- buspirone 13 . 2 ( avg ) 51 ( 5 . 62 ) ip 54 ( 5 . 62 ) po______________________________________ . sup . 1 ic . sub . 50 ( nmol ) . sup . 2 % time spent in lit area ( dose , mg / kg ip ), minimum effective dose the pharmaceutical compositions used in the methods of this invention for administration to living animals are comprised of , as active ingredients , at least one of the compounds of formula i according to this invention , in association with a pharmaceutical carrier or excipient . the compounds are thus presented in a therapeutic composition for oral , parenteral , or rectal administration . thus for example , compositions for oral administration can take the form of elixirs , capsules , tablets or coated tablets containing carriers conveniently used in the pharmaceutical art . suitable tableting excipients include lactose , potato and maize starches , talc , gelatin , stearic and silicic acids , magnesium stearate and polyvinyl pyrrolidones . for parenteral administration , the carrier or excipient can be comprised of a sterile parenterally acceptable liquid , e . g ., water or arachis oil contained in ampoules . in compositions for rectal administration , the carrier can be comprised of a suppository base , e . g ., cocoa butter or a glyceride . advantageously , the compositions are formulated as dosage units , each unit being adapted to supply a fixed dose of active ingredients . tablets , coated tablets , capsules , ampoules and suppositories are examples of preferred dosage forms according to the invention . it is only necessary that the active ingredient constitute an effective amount ; i . e ., such that a suitable dosage will be consistent with the dosage form employed in single or multiple unit doses . the exact individual dosages , as well as daily dosages , will , of course , be determined according to standard medical principles under the direction of a physician or veterinarian . generally , the pharmacology tests suggest a contemplated effective oral dose for humans will be in the range of 2 - 200 mg daily to be taken in divided doses of from 0 . 5 to 50 mg 3 to 4 times daily .
this invention discloses the antianxiety properties of compounds of the formula : ## str1 ## wherein n is 3 or 4 , r is c 1 - c 4 alkyl or phenyl , and ar is ## str2 ## where z is selected from h , c 1 - c 4 alkoxy , c 2 - c 4 alkenyloxy or hydroxy .