Patent ID: 9051291
Filing Date: 2015-06-09
Classification: C07C,C07D

Abstract:
1. A process for the preparation of (S)-equol (1) comprising: (a) reacting 4-hydroxy phenyl acetic acid and 2,4-dihydroxy benzaldehyde in presence of an acid anhydride and a base to provide 4-(7-acetoxy-2-oxo-2H-chromen-3-yl)phenyl acetate of formula (3) (b) hydrolyzing the acetyl groups of 4-(7-acetoxy-2-oxo-2H-chromen-3-yl)phenyl acetate of formula (3) in presence of a base to provide 7-hydroxy-3-(4-hydroxyphenyl)-2H-chromen-2-one of formula (4) (c) hydrogenating 7-hydroxy-3-(4-hydroxyphenyl)-2H-chromen-2-one of formula (4) to provide a mixture of 7-hydroxy-3-(4-hydroxyphenyl)-2H-chroman-2-one of formula (5) and methyl 3-(2,4-dihydroxyphenyl)-2-(4-hydroxyphenyl)propanoate of formula (6) (d) hydrolyzing the mixture of 7-hydroxy-3-(4-hydroxyphenyl)-2H-chroman-2-one of formula (5) and methyl 3-(2,4-dihydroxyphenyl)-2-(4-hydroxyphenyl)propanoate of formula (6) with a base to provide 3-(2,4-dihydroxyphenyl)-2-(4-hydroxyphenyl)-propanoic acid of formula (7) (e) resolving 3-(2,4-dihydroxyphenyl)-2-(4-hydroxyphenyl)propanoic acid of formula (7) to its corresponding (S)-isomer (7A) via diastereomeric salt formation with a chiral amine (f) reducing (S)-3-(2,4-dihydroxyphenyl)-2-(4-hydroxyphenyl)propanoic acid of formula (7A) to provide (S)-4-(3-hydroxy-2-(4-hydroxyohenyl)propyl)benzene-1,3-diol of formula (9) and (g) cyclizing (S)-4-(3-hydroxy-2-(4-hydroxyohenyl)propyl)benzene-1,3-diol of formula (8) to provide (S)-equol (1).