Patent ID: 7964739

Claim:
A process for preparing asenapine of Formula I, or a pharmaceutically acceptable salt thereof, wherein an E-stilbene derivative of Formula II, wherein R 1 is F, Br or I; R 2 and R 3 are different and are each selected from H and Cl; and R 4 is H or a hydroxyl protecting group; is reacted with an azomethine ylide generated from a precursor tertiary amine of Formula A wherein R 5 represents an amino protecting group of formula —CHXY, wherein: X is (C 1-6 )alkyl, vinyl (optionally substituted with halogen) or phenyl (optionally substituted with (C 1-3 )alkyl, (C 1-3 )alkoxy, NO 2 , CN or halogen); and Y is H or phenyl; or X is: COOR 6 wherein R 6 is (C 1-4 )alkyl; and Y is H, (C 1-6 )alkyl, phenyl or benzyl; to provide a trans-pyrrolidine derivative of Formula III, from which the hydroxyl protecting group R 4 , when present, is removed, and which is subsequently treated under conditions which effect an intramolecular ring closure reaction to yield the oxepino compound of Formula IV, whereupon the amino protecting group R 5 is replaced by a methyl group, and the resulting asenapine of Formula I is optionally converted into a pharmaceutically acceptable salt thereof.