1. Field of the Invention
This invention belongs to the field of synthetic organic chemistry, and provides a method of preparing certain substituted benzyl esters of phenylacetic acids, which process is carried out with the assistance of a phase transfer catalyst.
2. State of the Art
Phase transfer catalysts are used to assist in a number of types of organic reactions, and are usually used to facilitate reaction between one reagent which is dissolved in an aqueous phase, and another reagent dissolved in an organic phase. For example, U.S. Pat. No. 4,072,677, of Beecham Group Limited, shows the synthesis of certain penicillin esters by esterification in systems such as dichloromethane/water, using phase transfer catalysts (ptc) such as tetrabutylammonium bromide, cetyltrimethylammonium bromide and the like.
The use of ptc's has been taught by many commentators in the chemical literature. The compounds used as ptc's, in general, are either quaternary ammonium salts or crown ethers. The following references are typical.
Starks, Chemtech, 110-17 (Feb. 1980); PA1 Jones, Aldrichimica Acta 9, 35-45 (1976 No. 3); PA1 Hennis et al., I. and E.C. Prod. Res. and Dev. 7, 96-101 (1968). PA1 one of R.sup.2 and R.sup.3 is hydrogen and the other is phenoxy or C.sub.1 -C.sub.6 alkoxy; PA1 X.sup.1 is chloro, bromo, iodo, toluenesulfonate or methanesulfonate; PA1 R.sup.4 and R.sup.5 are independently C.sub.1 -C.sub.16 alkyl, phenyl or benzyl; PA1 R.sup.6 and R.sup.7 are independently C.sub.1 -C.sub.16 alkyl; PA1 (a) R.sup.1 is hydroxy or protected hydroxy; PA1 (b) R.sup.1 is hydroxy; PA1 (c) R.sup.1 is hydrogen; PA1 (d) M is potassium; PA1 (e) One of R.sup.2 and R.sup.3 is hydrogen and the other is C.sub.1 -C.sub.3 alkoxy; PA1 (f) One of R.sup.2 and R.sup.3 is hydrogen and the other is methoxy; PA1 (g) R.sup.2 is methoxy and R.sup.3 is hydrogen; PA1 (h) X is chloro; PA1 (i) The amount of the alkali metal iodide is from about 0.15 mole to about 0.4 mole per mole of product to be produced; f PA1 (j) The alkali metal iodide is a sodium or potassium iodide; PA1 (k) The solvent is an ester, a ketone or a nitrile; PA1 (l) The solvent is a ketone; PA1 (m) The solvent is acetone; PA1 (n) The amount of the ptc is from about 0.001 mole to about 0.1 mole per mole of product to be produced; PA1 (o) The ptc is a tetraalkylammonium chloride or bromide; PA1 (p) The ptc is a tetra(C.sub.1 -C.sub.8 alkyl)ammonium chloride or bromide. PA1 (a) Phenylacetic acid, sodium salt, is reacted with 4-methoxybenzyl bromide to obtain 4-methoxybenzyl phenylacetate; PA1 (b) 3-Butylphenylacetic acid, potassium salt, is reacted with 4-isopropoxybenzyl chloride to obtain 4-isopropoxybenzyl 3-butylphenylacetate; PA1 (c) 4-Chlorophenylacetic acid, sodium salt, is reacted with 2-methoxybenzyl bromide to obtain 2-methoxybenzyl 4-chlorophenylacetate.