Process for obtaining enantiomers of duloxetine precursors

摘要

The present invention is directed to a process for the preparation of an enantiomerically enriched compound of formula II
wherein,
R 1 , R 2 and R 3 are each independently selected from hydrogen, halogen, substituted or unsubstituted lower alkyl or substituted or unsubstituted aryl;
X is -C(=O)-Z or -Y, wherein -Y is selected from -CH 2 -OR 4 , -CH 2 -halogen or - CH 2 -NR 6 R 7 ;
wherein
Z is selected from -NR 6 R 7 or -OR 5 , wherein R 5 is selected from hydrogen, substituted or unsubstituted lower alkyl or ester activating group;
R 4 is selected from hydrogen, hydroxyl protecting group or hydroxyl activating group;
R 6 and R 7 are each independently selected from hydrogen, amino protecting group, amido protecting group or substituted or unsubstituted lower alkyl;
which comprises an enantioselective addition with a thienyl zinc reagent, in the presence of a chiral ligand.