申请人:CAFFARO S.p.A. Società per l'Industria
Chimica ed Elettrochimica
公开号:EP0645458A1
公开(公告)日:1995-03-29
A process for stereoselective (enantioselective) production of S-(-)-fenpropimorph, which process comprises reacting 4-tert-butylbenzylchloride or bromide with methyldiethylmalonate, decarbethoxylation of the product into racemic 3-(4-tert-butylphenyl)-2-methylpropionic acid ethyl ester in DMSO in the presence of alkali cations, then Pseudomonas sp. lipase catalyzed resolution of racemic ester to S-(-)-acid, base-catalyzed racemisation and recycling of the R-(+)-ester, acylation of cis-2,6-dimethylmorpholine with the activated derivative of S-(-)-acid, and final reduction of the intermediary amide to provide optically (enantiomerically) pure S-(-)-fenpropimorph. The key enzymatic reaction is fast, employs inexpensive commercially available enzyme, requires minimal work-up, and can therefore easily be performed on a large scale.
一种选择性立体异构体(对映选择性)生产S-(-)-芬普莫尔的过程,该过程包括将4-叔丁基苯甲基氯化物或溴化物与甲基二乙基丙二酸酯反应,将产物在DMSO中与碱金属阳离子存在下脱乙酰基成为外消旋的3-(4-叔丁基苯基)-2-甲基丙酸乙酯,然后通过假单胞菌脂肪酶催化将外消旋酯分离为S-(-)-酸,碱催化的消旋反应并回收R-(+)-酯,用激活的S-(-)-酸衍生物对顺式-2,6-二甲基吗啡进行酰化,最后还原中间酰胺以提供光学(对映)纯的S-(-)-芬普莫尔。关键的酶催化反应速度快,使用廉价的商业酶,需要最少的后处理工作,因此可以轻松地进行大规模生产。