the present flutroline intermediate , 2 - carbobenzoxy - 8 - fluoro - 5 -( p - fluorophenyl )- 2 , 3 , 4 , 5 - tetrahydro - 1h - pyrido [ 4 , 3 - b ] indole is prepared by the four steps , ( a ) to ( d ), which are defined above . the various step intermediates can be isolated , if desired . however , it is one of the features of the present highly efficient process to simply employ these intermediates in situ , avoiding the time consuming isolation and the inevitable loss of these valuable intermediates , while at the same time attaining the above flutroline intermediate in a high state of purity , suitable for further processing ( particularly processing which involves hydrogenation ) and ultimately yielding flutroline in the high state of a purity required for its use in therapy . step ( a ) of the present process , chlorination of 1 , 1 - di ( p - fluorophenyl ) urea , can be carried out by the action of substantially one equivalent of a ( c 1 - c 4 ) alkyl hypochlorite or a similar chlorinating agent . for reasons of mutual solubility in a common solvent , an alkyl hypochlorite is preferred ; for reasons of ready availability and solubility properties , t - butyl hypochlorite is most preferred . lower temperatures are generally used for the chlorination step , e . g ., - 10 ° to 10 ° c ., conveniently 0 °- 5 ° c . obtained by an ice - water bath . the preferred reaction - inert solvents are water - misible , readily dissolve both reactants , and are suitable for the further steps ( b ) to ( d ). especially well - suited are ( c 1 - c 3 ) alkanols , particularly methanol . step ( b ) involves rearrangement with loss of the elements of hcl and gain of the elements of ( c 1 - c 3 ) alkanol to form the intermediate carbalkoxy hydrazine . this step is readily accomplished by simple addition of substantially two equivalents of an alkali metal ( c 1 - c 3 ) alkoxide , conveniently sodium methoxide , maintaining the same reaction inert - solvent as used in step ( a ). the alkoxide is conveniently added at the temperature used for step ( a ). step ( b ) proceeds readily at moderate temperatures , e . g ., 0 °- 50 ° c ., and is conveniently carried out at ambient temperatures , usually in the range of about 17 °- 27 ° c . step ( c ), which involves base catalyzed hydrolysis and decarboxylation , is readily accomplished by simply adding excess water to the reaction mixture , otherwise maintaining the same reaction - inert solvent as used in steps ( a ) and ( b ). step ( c ) occurs most readily at somewhat higher temperature than steps ( a ) and ( b ), e . g ., 50 °- 100 ° c ., preferably about 60 °- 75 ° c . when the solvent boils below the desired reaction temperature , the solvent is partially removed by distillation , optionally with the addition of more water . alternatively , the reaction is carried out under pressure . step ( d ), formation of the desired carbobenzoxypyridoindole from the step ( c ) hydrazine and n - carbobenzoxy - 4 - piperidone involves initial formation of a hydrazone , which is followed by cyclization . if desired , the initial phase is accomplished simply by adding the piperidine and excess of a ( c 1 - c 4 ) alkanoic acid , preferably and conveniently acetic acid , to the hydrazine product of step ( c ), and warming to about 60 °- 110 ° c ., conveniently to reflux ( about 65 ° to 100 ° c ., depending upon the exact composition of solvents in the reaction mixture ). cyclization is then accomplished by adding an excess of a strong acid , preferably a strong mineral acid such as conc . hydrochloric acid , followed by further heating in the same elevated temperature range . alternatively and preferably , both hydrazone formation and cyclization are accomplished by heating in the strong acid , omitting the separate step in weak acid . the intermediate product , 2 - carbobenzoxy - 8 - fluoro - 5 -( p - fluorophenyl )- 2 , 3 , 4 , 5 - tetrahydro - 1h - pyrido [ 4 , 3 - b ] indole , is readily recovered by standard methods of solvent displacement , extraction , concentration and crystallization . generally , the above intermediate product is further processed by a hydrogenation step , either hydrogenation to 8 - fluoro - 5 -( p - fluorophenyl )- 2 , 3 , 4 , 5 - tetrahydro - 1h - pyrido [ 4 , 3 - b ] indole ( which can then be converted to flutroline by one of a number of methods , e . g ., see references cited above ), or hydrogenation in the presence of substantially one equivalent of the lactol , 2 -( p - fluorophenyl )- 5 - hydroxytetrahydrofuran , producing flutroline . in either case , the hydrogenation is carried out in a reaction - inert solvent , under a hydrogen atomsphere , in the presence of a hydrogenation catalyst such as nickel , or a noble metal . such catalysts are used in an amount sufficient to catalyze the process . as is well known in the art of catalytic hydrogenation , the amount of catalyst required will vary with the nature of the catalyst , the activity of a particular batch of catalyst and the exact conditions of the hydrogenation ( e . g ., the reactor , the type and amount of agitation , temperature , pressure , solvent ). while the amount of catalyst will be generally similar to the amounts which are illustrated in the examples below , routine experimentation will define optimal amounts in specific cases . the noble metal catalysts as employed in the present invention include platinum , palladium , rhenium , rhodium and ruthenium , either of the supported or non - supported type , as well as the known catalytic compounds thereof such as the oxides , chlorides , etc . examples of suitable catalyst supports include carbon , silica and barium sulfate . the catalysts may be preformed or formed in situ by reduction of an appropriate salt of the catalytic compound . examples of preferred catalysts are 5 % palladium - on - carbon , 5 % platinum - on - carbon , 5 % rhodium - on - carbon , platinum chloride , palladium chloride , platinum oxide and ruthenium oxide . the most highly preferred catalyst for reasons of economy and efficiency , is palladium , particularly palladium supported on carbon . the pressure of the present hydrogenation is not critical and can range from subatmospheric to 100 atmospheres , or higher . moderate pressures of about 2 - 8 atmospheres are preferred , since the hydrogenation generally proceeds at a reasonable rate at these pressures and the elaborate and expensive equipment required for higher pressure hydrogenation is avoided . the temperature of the hydrogenation is also not critical . temperatures ranging from 0 °- 75 ° c . are generally satisfactory . as a matter of convenience , ambient temperatures ( about 17 °- 27 ° c .) are usually preferred , the cost of cooling or heating thus being avoided . for the present hydrogenation processes , examples of suitable solvents are ( c 1 - c 3 ) alkyl acetates ; ( c 1 - 4 ) alkanols ; ethers such as dimethoxyethane , tetrahydrofuran , dioxane ; or isopropyl ether ; glycol or glycol monoethers such as 2 - methoxyethanol ; hydrocarbons such as benzene , toluene and xylene ; halocarbons such as methylene chloride or chloroform ; water ; or combinations of two or more of these solvents . the preferred solvent is either ethyl acetate , or a mixture of ethyl acetate and a ( c 1 - c 3 ) alkanol . flutroline ( per se or as a pharmaceutically - acceptable salt thereof ), as well as the present alternative flutroline intermediate also derived by hydrogenation , are recovered by standard methods of solvent displacement , extraction , concentration and crystallization which are well known in the art . the required 1 , 1 - di ( p - fluorophenyl ) urea is conveniently prepared from di ( p - fluorophenyl ) amine by the action of sodium cyanate in the presence of trifluoroacetic acid , following the method of murakami ( supra ). the di ( p - fluorophenyl ) amine is conveniently prepared by an improved ullman method , see j . org . chem . 26 , p . 2721 ( 1961 ). the required n - carbobenzoxy - 4 - piperidone is readily available by reaction of carbobenzyoxy chloride with 4 - piperidone under conditions well known in the art , or from n - benzyl - 4 - piperidone as specifically described below . finally , preparation of the requisite lactol is according to methods disclosed in u . s . pat . no . 4 , 267 , 331 ( supra ). the following examples are provided solely for the purpose of illustration and are not to be construed as limitations of the invention , many variations of which are possible without departing from the spirit or scope thereof . di ( p - fluorophenyl ) amine ( 102 . 5 g ., 0 . 5 mole ) and naocn ( 65 g , 1 . 0 mole ) were stirred in 700 ml ch 2 cl 2 at 16 ° c . f 3 ccooh ( 84 . 5 ml , 117 g , 1 . 025 mole ) was added as a thin stream over 5 minutes , during which the reaction mixture exothermed to 28 ° c . the exotherm peaked at 32 ° c . shortly after addition was complete . the reaction mixture was stirred at 23 °- 25 ° for 21 hours , diluted with 350 ml h 2 o and stirred 0 . 5 hour . the organic layer was separated and stirred 0 . 25 hour with 40 g naoh in 500 ml h 2 o . the layers were separated , and the aqueous layer back washed with 100 ml ch 2 cl 2 . the combined organic layer and back wash was dried ( mgso 4 ), concentrated to 600 ml , diluted with 600 ml isopropanol , reconcentrated to 600 ml , rediluted with 600 ml of fresh isopropanol , reconcentrated to 800 ml , rediluted with 400 ml fresh isopropanol and again reconcentrated to 800 ml . the mixture was cooled to room temperature ( product began to crystallize ) and then to 0 °- 5 ° c . title product was recovered by filtration , 104 . 9 g , m . p . 150 °- 153 ° c . t - butyl hypochlorite ( 7 . 5 g , 0 . 070 mole ) was added to 1 , 1 - di ( p - fluorophenyl ) urea ( 17 . 5 g , 0 . 071 mole ) in 440 ml methanol at 0 °- 5 ° and the mixture stirred for 1 hour at that temperature to produce a solution containing step ( a ) title product . at 0 °- 5 ° c . sodium methoxide ( 7 . 55 g , 0 . 14 mole ) in 100 ml of methanol was added to the solution of step ( a ) product . the mixture was stirred 0 . 5 hour at 0 °- 5 ° c . and 2 hours at ambient temperature to yield a solution of step ( b ) title product . water ( 100 ml ) was added to the solution of step ( b ) product and methanol removed by distillation until the pot temperature was 74 ° c . the mixture was then refluxed 16 hours and finally cooled to ambient temperature to yield a solution of step ( c ) title product . the solution from step ( c ) was diluted with 35 ml acetic acid and 16 . 2 grams ( 0 . 0695 mole ) of n - carbobenzoxy - 4 - piperidone was added . the reaction mixture was heated to reflux for 30 minutes , cooled to ambient temperature , acidified with 60 ml conc . hcl , and refluxed an additional 1 . 5 hours . after example 2 ( cont .) adding 100 ml of water , the solution was refluxed for 5 minutes and filtered hot . the solids were washed with water at 45 ° c ., followed by 50 ml of cold methanol , and then dissolved in 400 ml ch 2 cl 2 . the resulting solution was dried ( mgso 4 ), treated with activated charcoal and filtered . by repeated addition of methanol and distillation to a final pot temperature of 65 ° c . and a final volume of 200 ml , ch 2 cl 2 was displaced with methanol . the resulting slurry of step ( d ) title product was recovered by filtration , 17 . 8 g , m . p . 157 °- 160 ° c . anal . calcd for c 25 h 20 n 2 o 2 f 2 : c , 71 . 76 ; h , 4 . 82 ; n , 6 . 70 ; m / e 418 . found : c , 71 . 76 ; h , 4 . 91 ; n , 6 . 69 ; m / e 418 . t - butyl hypochlorite ( 22 . 8 g , 0 . 21 mole ) was added to 1 , 1 - di ( p - fluorophenyl ) urea ( 49 . 4 g , 0 . 2 mole ) in 750 ml methanol at 0 °- 5 ° and the mixture stirred for 0 . 5 hour to produce a thin slurry containing step ( a ) title product . at 0 °- 5 ° c ., sodium methoxide ( 22 . 7 g ) in 250 ml methanol was added in a thin stream over 5 minutes to the step ( a ) product mixture . the reaction mixture was warmed to 40 °- 45 ° c . for 15 minutes to produce a milky solution of step ( b ) title product . naoh ( 40 g ) in 175 ml h 2 o was added to the step ( b ) product mixture . the mixture was distilled at ambient pressure to remove the methanol and the aqueous residue refluxed for 25 hours and cooled to ambient temperature to yield a solution of step ( c ) title product . the solution from step ( c ) was diluted with 300 ml conc . hcl , maintaining 35 ° c . or less . n - carbobenzoxy - 4 - piperidone ( 46 . 6 g , 0 . 2 mole ) was added and the mixture heated to reflux for 1 hour . the resulting thick slurry was filtered hot with water and methanol wash , 64 . 6 g . the solids were taken into 400 ml chcl 2 , carbon treated , dried ( mgso 4 ), and the example 3 ( cont .) ch 2 cl 2 displaced with methanol to a final volume of 500 ml and purified step ( d ) title product recovered by filtration , 60 . 9 g , identical with title product of example 2 . in a parr bottle were combined 5 % pd / c ( 5 g of 50 % water - wet ), 8 - fluoro - 5 -( p - fluorophenyl )- 2 - carbobenzoxy - 2 , 3 , 4 , 5 - tetrahydro - 1h - pyrido [ 4 , 3 - b ] indole ( 5 . 0 g , 0 . 0119 mole ) in 100 ml ethyl acetate , and 5 . 5 grams ( 0 . 03 mole ) 5 -( p - fluorophenyl )- 2 - hydroxytetrahydrofuran in 100 ml ethyl acetate . the mixture was agitated and hydrogenated at 30 - 40 psig for 20 hours . the solution was filtered to recover catalyst , with ethyl acetate and ch 2 cl 2 wash . the filtrate and washes were concentrated in vacuo to a viscous oil . the oil was dissolved in 400 ml ethyl acetate and filtered . the solution was concentrated to an oil , diluted with 150 ml ether , and filtered to yield title product , 3 . 8 gm , m . p . 145 °- 149 ° c . in a parr bottle were combined 5 % pd / c ( 10 g of 50 % water - wet ) and 60 g of 8 - fluoro - 5 - p - fluorophenyl )- 2 - carbobenzoxy - 2 , 3 , 4 , 5 - tetrahydro - 1h - pyrido [ 4 , 3 - b ] indole ( 60 g , 0 . 143 mole ) in 400 ml ethyl acetate and 100 ml methanol and the mixture hydrogenated at 44 - 80 psig for 4 hours . catalyst was recovered by filtration and the filtrate evaporated to solids in vacuo . the residue taken into ch 2 cl 2 , carbon treated , dried ( na 2 so 4 ) and ch 2 cl 2 displaced with hexane by distillation to a final pot temperature of 70 ° c . the white , crystalline product was recovered by filtration , 35 . 6 g , m . p . 126 °- 129 ° c . n - benzyl - 4 - piperidone ( 122 . 2 g , 0 . 645 mole ) in 500 ml toluene was warmed to 45 ° c . benzyl chloroformate ( 130 ml , 155 g , 0 . 915 mole ) was added in a thin , steady stream , and the reaction mixture heated to reflux for 2 hours , cooled to ambient temperature , diluted with 250 ml h 2 o and stirred vigorously 0 . 5 hour . the organic layer was separated , washed 1 × 400 ml 6n hcl and then 1 × 100 ml saturated nacl , dried ( mgso 4 ), treated with activated carbon , and concentrated to an oil . the oil was distributed between 400 ml ethyl acetate and 400 ml of h 2 o containing 67 . 0 g nahso 3 , stirred 0 . 5 hour , and the aqueous layer separated , washed with 3 portions of ether , made basic with aqueous naoh and extracted with fresh ether . the ether layer was dried and reevaporated to yield purified title product as an oil , 136 . 1 g .