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

An improved process for the preparation 3-aryl-2-hydroxy propanoic acid derivatives of the formula (1)

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• where R1 represents hydrogen atom or (C1-C6)alkyl group and R2 represents (C1-C6)allyl group which comprises:
• (i). selectively benzylating L-tyrosine of the formula (10)
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• using benzyl chloride, CUSO4 and sodium hydroxide in a solvent to yield a compound of the formula (11),
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• (ii). diazotising the compound of the formula (11) in the presence of an acidic reagent and an organic solvent to produce compound of the formula (8a),
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• (iii). simultaneous etherification and esterification of compound of formula (8a) using alkylating agent in the presence of a base and a solvent to obtain crude compound of formula (9a) with ee>90%
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• wherein R1 represents hydrogen or lower alkyl group and R2 represents lower alkyl group,
• (iv). hydrolysing the crude compound of formula (9a) obtained in step (iii) above in polar solvents using aqueous alkali to produce compound of formula (9b) acid
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• wherein R1 represents hydrogen or lower alkyl group,
• (v). treating the compound of formula (9b) acid where R2 represents hydrogen or lower alkyl group with chiral base in the presence of solvent to produce chemically and chirally pure (ee>99%) salt of formula (12)
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• where R1 represents hydrogen or lower alkyl group and X represents chiral bases such as R(+)-α-methylbenzylamine, S(+) phenylglycinol, cinchonidine, ephidrine, N-octylglucaramine or N-methylglucaramine,
• (vi). if desired, recrystallising the compound of formula (12) obtained above in a solvent to produce highly pure compound of formula (12) where R1 represents hydrogen or lower alkyl group,
• (vii). converting the compound of formula (12) defined above using a solvent and an acid to pure compound of formula (9b),
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• where R1 represents hydrogen or lower alkyl group,
• (viii). esterifying the pure compound of formula (9b) defined above using alkylating agent in the presence of potassium carbonate, hydrochloric acid, sulfric acid, amberlite or amberlist to produce pure compound of formula (9c)
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• where R1 represents hydrogen or lower alkyl group and R2 represents lower alkyl group and
• (ix). debenzylating the compound of formula (9c) using aqueous alcohol in the presence of metal catalysts to yield pure compound of formula (1) where R1 represents hydrogen or lower alkyl group and R2 represents lower alkyl group.