Fluoxetine process from benzoylpropionic acid

Details Fluoxetine process from benzoylpropionic acid Fluoxetine process from benzoylpropionic acid

1998-06-22

1999-08-10

Killos, Paul J.

Organic compounds -- part of the class 532-570 series

Organic compounds

Amino nitrogen containing

564356, 549322, 549326, 544 88, C07C21300

Patent

active

059361247

ABSTRACT:
A synthesis of fluoxetine is disclosed. The process begins with a lower alkyl ester of 3-benzoylpropionic acid, which is reduced in the presence of a chiral ligand to produce the corresponding .gamma.-hydroxy ester, and the ester is cleaved. The free acid is then condensed with the alcohol to form a .gamma.-lactone, which is treated with ammonia to provide the .gamma.-hydroxy amide. The amide undergoes a Hoffman rearrangement to provide a 2-oxo-1,3 oxazine, which is reduced to 3-(methylamino)-1-phenyl-1-propanol. The alcohol is deprotonated and reacted with a 4-chloro- or 4-fluoro benzotrifluoride to provide fluoxetine free base.

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