Methods for Preparing O-Desmethylvenlafaxine
The present invention provides an efficient method of making O-desmethyl-venlafaxine.
1 . A method of preparing O-desmethylvenlafaxine which comprises reacting venlafaxine with a high molecular weight alkane or arene thiolate anion in an alcohol, ethylene glycol, ether of ethylene glycol, or mixture thereof, to provide O-desmethylvenlafaxine.
2 . The method of claim 1 wherein the reaction is performed at about 150° C. to about 220° C.
3 . The method of claim 1 wherein the reaction is carried out for about 2 to about 5 hours.
4 . The method of claim 1 wherein the thiolate anion is a straight or branched chain alkane thiolate anion having 8 to 20 carbon atoms.
5 . The method of claim 1 wherein the thiol is an arene thiolate anion having from 6 to 10 carbon atoms.
6 . The method of claim 4 wherein the alkane thiolate anion is dodecanethiolate.
7 . The method of claim 5 wherein the arene thiolate anion is benzenethiolate.
8 . The method of claim 1 wherein the thiolate anion is generated in the presence of an alkoxide.
9 . The method of claim 8 wherein the alkoxide is methoxide.
10 . The method of claim 2 wherein the reaction is performed at from about 170° C. to about 220° C.
11 . The method of claim 2 wherein the reaction is performed at from about 180° C. to about 200° C.
12 . The method of claim 1 further comprising neutralizing the product to the isoelectric point in the presence of an alcohol comprising a straight or branched chain alkyl group of from 1 to 6 carbon atoms.
13 . The method of claim 12 wherein the alcohol is isopropanol.
14 . The method of claim 12 wherein the isoelectric point is about pH9.5 to about pH10.
15 . A method of preparing O-desmethylvenlafaxine which comprises the steps of demethylating venlafaxine with dodecyl thiolate and polyethylene glycol 400 in the presence of sodium methylate in methanol at about 180° C. to about 200° C. for about 2 to about 5 hours; and neutralizing the product to about pH 9.5 in the presence of isopropanol.