多西他赛C13侧链(4S,5R)-3-叔丁氧羰基-2-(4-甲氧基苯基)-4-苯基-1,3-噁唑烷-5-甲酸的合成

Synthesis of Docetaxel C13 Side Chain(4S,5R)-3-(tert-Butoxycarbonyl)-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidinyl-5-carboxylic Acid

报道了一条可用于工业生产的多西他赛C13侧链(4S,5R)-3-叔丁氧羰基-2-(4-甲氧基苯基)-4-苯基-1,3-噁唑烷-5-甲酸(1)的合成工艺。(2R,3S)-N-叔丁氧羰基-3-苯基异丝氨酸甲酯(2)与4-甲氧基苯甲醛二甲缩醛环化得(4S,5R)-3-叔丁氧羰基-2-(4-甲氧基苯基)-4-苯基-1,3-噁唑烷-5-甲酸甲酯,经氢氧化钠水解后,用阳离子交换树脂进行后处理得1,总收率78%(以2计),纯度99%。

A synthetic process for docetaxel C13 side chain （4S,5R） -3-（tert-butoxycarbonyl） -2-（4- methoxyphenyl） -4-phenyl- 1,3-oxazolidinyl-5-carboxylic acid （1） was reported. Methyl （2R,3S） -N- （tert- butoxycarbonyl）-3-phenylisoserinate （2） reacted with 4-methoxybenzaldehyde dimethyl acetal to give methyl （4S,5R）- 3- （tert-butoxycarbonyl） -2- （4-methoxyphenyl） -4-phenyl-l,3-oxazolidinyl-5-carboxylate, which was purified by recrystallization in ethyl acetate/cyclohexane. The latter was subjected to hydrolysis with sodium hydroxide and then acidification by cation exchange resin to afford the target compound 1 with a total yield of 78 % （based on 2） and a purity of 99%.