3,3-Difluoropyrrolidine synthesis

Yield:-

Reaction Conditions:

with hydrogenchloride in diethyl ether;ethyl acetate at 20; for 3 h;

Steps:

ZS
To a solution of 3-OXO-PYRROLIDINE-1-CARBOXYLIC acid ter-butyl ester (1G) in CH2CI2 (10ML) is added [bis (2-methoxyethyl) amino] sulfer trifluoride (2mL) at 0C, and stirred for 11 HR at room temperature. The reaction mixture is poured in aqueous NaHC03 and extracted with Et20. The organic layer is successively washed with H20 and aqueous NACI, dried over MgS04, and concentrated in vacuo. The residue is purified by column chromatography to give a colorless oil. To a solution of the oil in ET20 (1 OmL) was added HCI in EtOAc (4N, 5mL) and stirred for 3hr at room temperature. The reaction mixture is concentrated in vacuo, and the residue is suspended in Et20. White precipitate in the Et20 is collected by filtration to to provide the title compound.

References:

NOVARTIS AG;NOVARTIS PHARMA GMBH WO2004/69256, 2004, A1 Location in patent:Page/Page column 49