process for the stereoselective synthesis of one (4s or 4r) -4-benzyl-3- 2r or 2s - (1-hydroxycycloexyl) - (methoxyphenyl) acetyl -1,3-oxazolidin-2-one and one enantiomer of a 2-phenyl-2- (1-hydroxycycloalkyl) ethylamine or its salt and compounds

摘要

PROCESS FOR THE STEREOSELECTIVE SYNTHESIS OF ONE (4S OR 4R) -4-BENZYL-3- [2R OR 25) - (1-HYDROXYCYCLEEXYL) - (METHYXYphenyl) ACETYL] -l, 3-OXAZOLIDIN-2-ONA AND OF AN ENANTHYMER OF A 2-PHENYL-2- (1- HYDROXYCYCLEALKYL) ETHYLAMINE OR ITS SALT AND COMPOUNDS A process for the enantioselective synthesis of a (5) - or (R) -1 - [(2-dimethylamino) - l- is described (methoxyphenyl) ethyl] cyclohexanol and its analogs or salts. The method involves the steps of (a) reaction of a (5) - or (R -4-benzyloxazolidinone with a mixed anhydride of a methoxyphenylacetic acid, under conditions that form an oxazolidinone, (4S) - or (4R) -4- benzyl-3- [(methoxyphenyl) acetill-oxazolidin-2 - one; (b) treatment of (4S) - or (4R) -4-benzyl-3 - [(methoxyphenyl) acetylJ-1,3-oxazolidin-2 -one with an aprotic amine base and titanium chloride in a chlorinated solvent, under conditions that allow the formation of the corresponding anion; (c) mixing of the corresponding anion with titanium chloride and cyclohexanone, under conditions that allow an aldol reaction form (4S) - or (4R) -4-benzyl-3-- E (2R) -2- (1-hydroxycyclohexyl) -2- (methoxy-phenyl) acetyl] -1, 3-oxazolidin-2-one (d) hydrolysis of (4S) - or (4R) -4-benzyl-3 - [(2R) -2- (1-hydroxycyclohexyl) -2- (methoxyphenyl) acetyl] -1,3-oxazo-lidin -2-one to form a chiral (2R or 2S) - (1-hydroxycyclohexyl) methoxyphenyl) acetic acid; (e) coupling the chiral phenylacetic acid to a secondary amine, to form an amide; and (f) reducing the amide to form an (S) - or (R) -1 - {(2-dimethylamino) -1- (methoxyphenyl) ethyl] cyclohexanol or its salt.