[EN] PROCESS FOR PRODUCING OPTICALLY ACTIVE 3-(4-HYDROXYPHENYL)PROPIONIC ACIDS<br/>[FR] PROCEDE DE PRODUCTION D'ACIDES 3-(4-HYDROXYPHENYL)PROPIONIQUES OPTIQUEMENT ACTIFS
申请人:TAKASAGO PERFUMERY CO LTD
公开号:WO2005051882A1
公开(公告)日:2005-06-09
The present invention relates to a process for producing an optically active 3-(4-hydroxyphenyl)propionic acid useful as intermediates for medicines, through short steps in good yield and with high optical purity. More specifically, the present invention relates to a process for producing an optically active 3-(4-hydroxyphenyl)propionic acid of the formula (6): wherein R2 is an alkyl group; R5 to R8 are each independently a hydrogen atom or a substituent; and the symbol * is an chiral carbon atom, or a salt thereof, which comprises reacting a benzaldehyde of the formula (1): wherein R1 is a protective group; and R5 to R8 are each the same as defined above, with a glycolic acid derivative of the formula (2): wherein R3 is a hydrocarbon group; and R2 is the same as defined above, hydrolyzing the resulting product to give a cinnamic acid of the formula (4): wherein R1, R2 and R5 to R8 are each the same as defined above, or a salt thereof, and subjecting the resulting cinnamic acid (4) or a salt thereof to asymmetric hydrogenation to give an optically active phenylpropionic acid of the formula (5): wherein all the symbols are each the same as defined above, or a salt thereof, followed by deprotection.
本发明涉及一种生产光学活性3-(4-羟基苯基)丙酸的工艺,作为药物中间体,通过简短的步骤、高产率和高光学纯度。更具体地,本发明涉及一种生产光学活性3-(4-羟基苯基)丙酸的工艺,其化学结构如下(6):其中R2是烷基;R5至R8分别独立地是氢原子或取代基;符号*是一个手性碳原子,或其盐,包括将化学结构如下(1)的苯甲醛:其中R1是保护基;R5至R8分别与上述定义相同,与化学结构如下(2)的甘醇酸衍生物反应:其中R3是烃基;R2与上述定义相同,水解得到肉桂酸的产物:其中R1、R2和R5至R8分别与上述定义相同,或其盐,并将得到的肉桂酸(4)或其盐进行不对称氢化反应,得到光学活性苯丙酸的产物:其中所有符号均与上述定义相同,或其盐,随后进行去保护处理。