Patent ID: 6051707
Filing Date: 2000-04-18
Classification: C07D

Abstract:
A process for the preparation of 2-(R)-(1-(R)-(3,5-bis(trifluoro-methyl)phenyl)-ethoxy)-4-(5-(dimethylamino )methyl-1,2,3-triazol-4-yl)methyl-3-(S)-(4-fluorophenyl)-morpholine which comprises:(a) reacting in the presence of a base 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)-ethoxy)-3-(S)-(4-fluoropheny l)morpholine with an alkylating agent selected from propargyl bromide and propargyl iodide in an organic solvent to give 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)-ethoxy)-3-(S)-(4-fluoropheny l)-4-propargylmorpholine;(b) reacting 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl) phenyl)-ethoxy)-3-(S)-(4-fluorophenyl)-4-propargylmorpholine in an organic solvent with an organometallic base followed by dimethyl formamide to give 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)-ethoxy)-3-(S)-4-(4-oxo-but-2 -ynyl-(4-fluorophenyl)morpholine;(c) reacting 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl) phenyl)-ethoxy)-3-(S)-4-(4-oxo-but-2-ynyl-(4-fluorophenyl)morpholine with sodium azide to give 2-(R)-(1-(R)-(3,5-bis(trifluoro-methyl)phenyl)-ethoxy)-4-(5-oxomethyl-1,2, 3-triazol-4-yl)methyl-3-(S)-(4-fluorophenyl)morpholine; and(d) reductive amination of 2-(R)-(1-(R)-(3,5-bis (trifluoro-methyl)phenyl)-ethoxy)-4-(5-oxomethyl-1,2,3-triazol-4-yl)methyl -3-(S)-(4-fluorophenyl)morpholine with dimethyl amine to give 2-(R)-(1-(R)-(3,5-bis(trifluoro-methyl)phenyl)-ethoxy)-4-(5-(dimethylamino )methyl-1,2,3-triazol-4-yl)methyl-3-(S)-(4-fluorophenyl)morpholine.