1-Pyrrolidinecarboxylic acid, 4-aMino-2-(difluoroMethyl)-, 1,1-d synthesis

Yield: 76%

Reaction Conditions:

with triphenylphosphine in tetrahydrofuran;water at 20; for 72 h;

Steps:

25
Preparation of compound 25f: tert-butyl (2S,4/?)-4-amino-2- (difluoromethyl)pyrrolidine-i -carboxylateA solution of 25e (1.5 g, 0.0057 mol) and PPh₃ (3.0 g, 0.0114 mol) in THF (50 ml_) and water (5 ml_) was stirred at room temperature for 72 h. The reaction mixture was concentrated in vacuo to give residue, which was dissolved in EtOAc (50 ml_). The EtOAc layer was acidified with 5% aqueous citric acid to pH ~ 4. The separated aqueous layer was extracted with EtOAc (50 ml_^χ3) and then basified with solid NaHCO3 to pH ~8, The basified aqueous layer was extracted with dichloromethane (50 ml_^χ3). The combined dichloromethane layers were dried over Na₂SO₄ and concentrated in vacuo which gave the title compound 25f as yellow oil (1.0 g, 76%).

References:

PFIZER INC.;NINKOVIC, Sacha;BRAGANZA, John Frederick;COLLINS, Michael Raymond;KATH, John Charles;LI, Hui;RICHTER, Daniel Tyler WO2010/16005, 2010, A1 Location in patent:Page/Page column 120; 122