Patent ID: 6184005
Filing Date: 2001-02-06
Classification: C07D

Abstract:
A process for the preparation of (-)-3,4-trans-compounds of the formula I ##STR30##wherein R.sup.1 and R.sup.4 are individually hydrogen, C.sub.1-6 alkyl or C.sub.1-6 alkoxy, R.sup.5 is --O--(CH.sub.2).sub.n --NR.sup.6 R.sup.7 wherein n is an integer in the range of 1 to 6 and R.sup.6 and R.sup.7 independently are C.sub.1 6 alkyl or R.sup.6 and R.sup.7 together with the N atom is a saturated or unsaturated 5- or 6-membered heterocyclic group containing one or two heteroatom(s) which heterocyclic group is optionally substituted with C.sub.1-6 alkyl; and R.sup.2 and R.sup.3 are individually hydrogen or C.sub.1-6 alkyl; or a salt thereof, which comprisesa) treating a cis-racemate of a compound of formula V ##STR31##or a salt thereof, wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are as defined above with an agent of formula R--CO--X, wherein R is C.sub.1-12 alkyl, optionally substituted with C.sub.1-6 alkyl, C.sub.1-6 alkoxy, hetaryl or aryl or C.sub.1-12 alkoxy, optionally substituted with C.sub.1-6 alkyl, C.sub.1-6 alkoxy, hetaryl or aryl, and X is a leaving group, thereby providing a cis-racemate of a compound of formula VI ##STR32##or a salt thereof, wherein R, R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are as defined above,b) treating said cis-racemate of formula VI with an enzyme having lipase activity, thereby providing a mixture comprising a compound of formula VIa ##STR33##or a salt thereof, and a compound of formula VII ##STR34##or a salt thereof,or a mixture comprising a compound of formula VIb ##STR35##or a salt thereof, and a compound of formula VIIa ##STR36##or a salt thereof,c) separating said mixture of compound VIa and VII or said mixture of compound VIb and VIIa, thereby obtaining a compound of formula VII or a compound of formula VIb, which compound VIb is then hydrolyzed to said compound of formula VII,d) treating said compound of formula VII or a salt thereof, with an agent of formula Y--R.sup.5 wherein Y is leaving group, thereby providing a compound of formula VIII ##STR37##or a salt thereof,e) treating said compound of formula VIII or a salt thereof with a strong base in an aprotic solvent, thereby obtaining said compound of formula I or a salt thereof.