CS195615B1 - Method of producing derivatives of 3-hydroxy-2-phenylpropionic acid - Google Patents

Description

DESCRIPTION COMPLETED WITH COPYRIGHT CERTIFICATE

CZECHOSLOVAKCASOCIALISTREPUBLIC (1 ») 195615 (11) (Bl)

/ 22 / Registered 12 04 78/21 / / PV 2385-78 / (, | HI Published 31 05 79

OFFICE OFFICE (45) Issued 1 5 04 8 2

AND DISCOVERY (75) -

Author of the Invention FIŠNEROVÁ LUDMILA ing. CSc. and NĚMEČEK OLDŘICH dr. DrSc., PVAHA (54) Method of production of 3-hydroxy-2-phenylpropionic acid derivatives

BACKGROUND OF THE INVENTION The present invention relates to a process for the preparation of novel derivatives of 3-hydroxy-2-phenylpropionic acid of general formula I, -A-c, R 1, J 2, CHCOOCaH 5 (III),

HCOOH

CH 3 OH in which R represents a chlorine atom, an isopropyl or isobutyl group. The compounds of this general formula are key intermediates in the synthesis of 1-p-chlorobenzoyl-5-methoxy-2-methyl-3-indolylacetic acid esters, which are significantly. for the purpose of the Act No. 195 614 /.

According to the invention, the novel derivatives of general formula X are prepared by taking the ethyl esters of phenylacetic acid of the formula II R '11Z'

wherein R is the same as in Formula I, the paraformaldehyde for introducing the hydroxymethyl group into the e-position of the carboxyl group of Formula II, in the presence of an alcoholate of an alkali, preferably sodium ethylate, in an inert organic solvent for example dimethylsulfoxide and the resulting ethyl ester of formula III wherein R is the same as in formula I, for example by boiling with an ethanolic solution of sodium hydroxide. The starting ethyl esters of phenylacetic acid of formula (II) are those known to be prepared by procedures known in the art.

Further details of the process according to the invention can be seen in the following examples, which are merely illustrative but not limiting. Example!

To a mixture of 21 g of ethyl-p-chlorophenylacetic acid and 3.15 g of paraformaldehyde in 115 ml of anhydrous dimethyl sulfoxide, 11.5 ml of 0.5 M ethanolic sodium ethylate solution are added with stirring. Stirring was continued for 30 minutes, the reaction was acidified with acetic acid, the dimethyl sulfoxide was distilled off under reduced pressure, and the residue was distilled to give 11.95 g of pure ester, mp 125-128 ° C / 66 Pa. This amount of ester is heated with ethanolic hydroxide solution prepared from 1.23 g of sodium, 37 ml of methanol and 1.43 ml of water, and boiled for 5 minutes at room temperature. Excluded acid salt (4 g / s) 195615

Claims (3)

195615 is aspirated, dissolved in minimal amounts of water and the acid is liberated by acidification with dilute hydrochloric acid. 3 g of 3-hydroxy-2-p-chlorophenylpropionic acid are obtained, m.p. 140 DEG-142 DEG C. (toluene). Example 2 As in Example 1, 20 g of p-isopropylphenylacetic acid ethyl ester are prepared with 15.68 g of the ethyl ester of the corresponding hydroxymethyl acid, m.p. 131-132 ° C / 53 Pa. Hydrolysis of the ester yields 8.3 g of the sodium salt, 6.14 g of pure 3-hydroxy-2-isopropylpentylphenylpropionic acid is obtained from the aqueous solution of which is acidified, extracted with ether, dried and concentrated to dryness. 99 DEG-100 DEG C. (cyclohexane). Example 3. As in Example 1, 10 g of crude p-isobutyl enylacetic acid are prepared with 10 g of crude hydroxymethyl ester which is hydrolyzed in the crude state. The acid released by acidification of the aqueous solution with 5.65 g of salt is extracted into ether and concentrated to dryness to give 3.35 g of pure 3-hydroxy-2-p-isobutylphenyl-propionic acid, mp 100-103 ° c / cyclohexane. SUMMARY OF THE INVENTION A process for preparing 3-hydroxy-2-phenylpropionic acid derivatives of formula R wherein R is chloro, isopropyl or isobutyl, characterized in that paraformaldehyde is applied to the phenylacetic acid ethyl ester of formula II wherein R is the same as in formula I to introduce a hydroxymethyl group at the oC-position of the carboxyl group of the compound of Formula II, in the presence of an alcoholate of an alkali metal, preferably sodium ethylate, in an inert organic solvent, for example dimethylsulfoxide, and the resulting ethyl ester of formula III CHCOOClH 2 OHOHR CH 2 C 2 C 2 H 5 (11) in which R represents the same as in Formula X, for example by boiling with an ethanolic solution of sodium hydroxide. Severografia. n. p. zivod 7. Most