Sodium Bicarbonate → (4S,5R)-5-[3,5-Bis(trifluoromethyl)phenyl]-3-{[3-bromo-6-(3-fluoroazetidin-1-yl)pyridin-2-yl]methyl}-4-methyl-1,3-oxazolidin-2-one

Participants

Reaction Conditions

Reaction Steps

To a solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(3-bromo-6-chloropyridin-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one (INTERMEDIATE 24, 2.0 g, 3.86 mmol) in DMSO (25 mL), under nitrogen, were added 3-fluoroazetidine hydrochloride (2.16 g, 19.3 mmol) and sodium bicarbonate (1.95 g, 23.2 mmol). The resulting mixture was stirred at 150° C. overnight. The reaction mixture was quenched with water, then extracted 3 times with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with ethyl acetate in hexanes to afford the titled compound. 1H NMR (500 MHz, CDCl3): δ 7.92 (s, 1H); 7.81 (s, 2H); 7.60 (d, J=8.5 Hz, 1H); 6.20 (d, J=8.6 Hz, 1H); 5.79 (d, J=8.6 Hz, 1H); 5.52 (m, 0.5H); 5.40 (m, 0.5H); 4.90 (d, J=16.9 Hz, 1H); 4.40-4.24 (m, 4H); 4.20-4.09 (m, 2H); 0.82 (d, J=6.6 Hz, 3H).

Provenance & Evidence