Patent ID: 6323345
Filing Date: 2001-11-27
Classification: A61P,C07C,C07D

Abstract:
A method of preparing 1-{2-[4-(6-methoxy-2-phenyl-1,2,3,4-tetrahydronaphthalene-1-yl)phenoxy]eth yl}pyrrolidine which comprises the steps of:1) brominating 2-bromo-5-methoxy-toluene to provide 1-bromo-2-bromomethyl-4-methoxybenzene;2) using the product of step 1 to alkylate ethyl benzoyl acetate, followed by decarboxylation to provide 3-(2-bromo-5-methoxyphenyl)-1-phenyl-propan-1-one;3) reacting the product of step 2 with ethylene glycol to produce 2-[2-(2-bromo-5-methoxyphenyl)-ethyl]-2-phenyl)-[1,3]dioxolane;4) treating the product of step 3 with n-butyl lithium and reacting with 4-benzyloxy benzonitrile to produce (4-benzyloxy-phenyl)-{4-methoxy-2-[2-(2-phenyl-[1,3]dioxolan-2-yl)-ethyl]- phenyl}-methanone, which is hydrolyzed to produce 3-[2-(4-benzyloxy-benzoyl )-5-methoxyphenyl]-1-phenyl-propan-1-one;5) treating the product of step 4 with titanium (III) chloride and zinc-copper couple to produce 4-(4-benzyloxyphenyl)-7-methoxy-3-phenyl-1,2-dihydronaphthalene; and6) hydrogenating the product of step 5 and treating with triphenyl phosphine, DEAD and 1-(2-hydroxyethyl)pyrolidine to produce 1-{2-[4-(6-methoxy-2-phenyl-1,2,3,4-tetrahydronaphthalene-1-yl)phenoxy]-et hyl}-pyrrolidine.