摘要
研究了雷米普利关键中间体2-苯甲酰氨基-3(2-氧代环戊基)丙酸甲酯的合成工艺,以丝氨酸为起始原料,经羧酸的酯化反应,苯甲酰氯酰化反应,酯基消除反应,以及迈克尔加成反应合成目标产物2-苯甲酰氨基-3(2-氧代环戊基)丙酸甲酯。重点考察了酰化反应和酯基消除反应的影响因素。结果表明,酰化反应的较优反应条件为:以乙酸乙酯作为溶剂,三乙胺作为碱;酯基消除反应的较优条件为:以甲醇为溶剂,碱DBU与2-苯甲酰氨基-3-甲氧基-3-氧代丙醇苯甲酸酯的投料摩尔比为1.5。该工艺总收率达到42%,收率较高、操作简便、环境友好,具有一定的产业化价值。
The paper studied the synthesis technology of the key intermediate of ramipril, methyl 2-benzamido-3-(2-oxocyclopentyl)propanoate. The target product methyl 2-benzamido-3-(2-oxocyclopentyl) propanoate was obtained using serine as starting materials from esterification reaction of carboxylic acid, acylation reaction of benzoyl chloride, ester group elimination reaction and Michael addition reaction, mainly focused on the influence factors of acylation reaction and ester group elimination reaction. The results showed that the optimal reaction conditions of acylation reaction were: ethyl acetate as solvent, triethylamine as base; the optimal reaction conditions of ester group elimination reaction were: methanol as solvent, mole ratio of alkali DBU with 2-benzamido-3-methoxy-3-oxopropanol benzoate was 1.5. The total yield was 42%. The synthesis technology had higher yield, simple process,friendly environment and had certain value for industrialization.
出处
《化工生产与技术》
CAS
2016年第1期31-34,8,共4页
Chemical Production and Technology
