SYNTHESIS OF 3-[4-(1,1-DIMETHYL-PROPYL)-PHENYL]-2-METHYL-PROPIONALDEHYDE AND cis-4--2,6-DIMETHYL-MORPHOLINE (AMOROLFINE)
申请人:BOITEAU JEAN-GUY
公开号:US20090131660A1
公开(公告)日:2009-05-21
3-[4-(1,1-Dimethyl-propyl)-phenyl]-2-methyl-propionaldehyde and cis-4-3-[4-(1,1-dimethyl-propyl)-phenyl]-2-methyl-propyl}-2,6-dimethyl-morpholine (Amorolfine) are synthesized, first by Heck reacting a compound of general formula (VI):
with 2-methyl-prop-2-en-1-ol of formula (VII):
in the presence of a palladium catalyst and a base, in a solvent selected from among N,N-dimethylformamide, polar protic and non-polar organic solvents, and at a temperature ranging from 60° C. to 150° C., and then conducting an amino reduction by reacting the 3-[4-(1,1-dimethyl-propyl)-phenyl]-2-methyl-propionaldehyde of formula (II) with cis-2,6-dimethyl morpholine of formula (IV):
in the presence of a reducing agent and in a solvent.
3-[4-(1,1-二甲基丙基)-苯基]-2-甲基-丙醛和顺式-4-3-[4-(1,1-二甲基丙基)-苯基]-2-甲基-丙基}-2,6-二甲基吗啡啉(阿莫罗芬)是通过首先在存在钯催化剂和碱以及选择自N,N-二甲基甲酰胺,极性质子和非极性有机溶剂之一的溶剂下,以60°C至150°C的温度范围内,使化合物的通用公式(VI)与化学式为(VII)的2-甲基-2-烯-1-醇进行Heck反应合成的,然后在存在还原剂和溶剂下,通过将化学式为(II)的3-[4-(1,1-二甲基丙基)-苯基]-2-甲基-丙醛与化学式为(IV)的顺式-2,6-二甲基吗啡啉进行氨基还原反应合成的。