Process for the preparation of 3-aryl-2-hydroxy propanoic acid compounds

Patent metadata

Field	Value
Publication number	US-9550719-B2
Application number	US-201414890008-A
Country	US
Kind code	B2
Filing date	May 9, 2014
Priority date	May 9, 2013
Publication date	Jan 24, 2017
Grant date	Jan 24, 2017

Abstract

The present disclosure provides a process for synthesis of 3-aryl-2-hydroxy propanoic acid derivatives of formula (S)-1. wherein R 1 represents H or (C 1 -C 5 ) alkyl groups and R 2 represents (C 1 -C 5 ) alkyl groups.

First claim

We claim:

1. A process for the preparation of 3-aryl-2-hydroxy propanoic acid compounds of formula (S)-1, wherein R 1 represents H or (C 1 -C 5 ) alkyl groups and R 2 represents (C 1 -C 5 ) alkyl groups, comprising the steps of;

a) subjecting an epoxide (S)-2 to regioselective ring opening with 4-methoxyphenylmagnesium bromide in presence of copper iodide to obtain a secondary alcohol (S)-3;

b) O-alkylating the secondary alcohol (S)-3 using ethyl iodide and a base in anhydrous DMF to give ethylated derivative (S)-4;

c) debenzylating (S)-4 in presence of a debenzylating agent to obtain primary hydroxy compound (S)-5;

d. oxidizing the compound (S)-5 in presence of an oxidizing agent to obtain compound (S)-6; and

e. demethylating the compound (S)-6 using sodium ethanethiolate to obtain (S)-7 followed by esterification using EtOH and HCl to give (S)-1a;
f. optionally, esterificating of (S)-7 as obtained in step (e) using anhydrous 2-propanol and SOCl 2 to give (S)-1b.

2. The process according to claim 1 , wherein the base used in step (b) is selected from NaOH, KOH, Na 2 CO 3 , or NaHCO 3 .

3. The process according to claim 1 , wherein the debenzylating agent used in step (c) is selected from Pd/C, Pd(OH) 2 , Raney-Ni or TiCl 4 along with dichloromethane.

4. The process according to claim 1 , wherein the oxidizing agent used in step (d) is selected from chromium trioxide along with H 2 SO 4 or sodium chlorite along with TEMPO and sodium hypochlorite.

5. The process according to claim 1 , wherein the compound of (S)-1a is ethyl (2S)-2-ethoxy-3-(4-hydroxyphenyl)propanoate,

6. The process according to claim 1 , wherein the compound of (S)-1b is isopropyl (2S)-2-ethoxy-3-(4-hydroxyphenyl)propanoate,

7. The process according to claim 1 , wherein overall yield of compound of (S)-1a is in the range of 40-45%.

8. The process according to claim 1 , wherein overall yield of compound of (S)-1b is in the range of 40-45%.

9. The process according to claim 1 , wherein enantiomeric excess (ee) of 3-aryl-2-hydroxy propanoic acid compounds of formula (S)-1 is in the range of 97-99%.

Assignees

• Council Scient Ind Res

Inventors

• Murugan Muthukrishnan
• Mohammad Mujahid

Classifications

• C07C41/09

  by dehydration of compounds containing hydroxy groups · CPC title

• C07C41/02

  from oxiranes · CPC title

• C07C51/29

  with halogen-containing compounds which may be formed in situ · CPC title

• C07C67/14

  from carboxylic acid halides · CPC title

• C07C41/26

  by introduction of hydroxy or O-metal groups · CPC title