Pyrrolidine → (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-[2-(1-pyrrolidin-1-ylpropyl)-5-(trifluoromethyl)benzyl]-1,3-oxazolidin-2-one

Participants

Reaction Steps

To a solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-(1-bromopropyl)-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazolidin-2-one (67.1 mg, 0.106 mmol) in MeCN (200 μL) was added pyrrolidine (1 mL, 12.0 mmol). The reaction was stirred at room temperature for 16 hours and then purified by reverse-phase chromatography (C-18, 10 to 95% MeCN/water with 0.1% TFA). The resulting solution was diluted with EtOAc (25 mL), washed with 1 M NaHCO3 (20 mL), extracted with EtOAc (25 mL), and washed with brine (20 mL). The organic layer was dried over Na2SO4, filtered, and concentrated. To the residue was added 200 μL CDCl3, which resulted in a mixture that was diluted with CH2Cl2 (20 mL) and water (5 mL), and washed with 1 M NaOH solution (5 mL). The organic layer was dried over Na2SO4, filtered, and concentrated to afford (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-[2-(1-pyrrolidin-1-ylpropyl)-5-(trifluoromethyl)benzyl]-1,3-oxazolidin-2-one. Rf=0.14 (25% EtOAc/hexanes). LCMS=583.3 (M+1)+. 1H NMR (CDCl3, 500 MHz, diastereomers present) δ 7.94 (s, 1H), 7.84 (s, 2H), 7.67-7.48 (m, 3H), 5.70-5.68 (m, 1H), 5.08-4.96 (m, 1H), 4.64-3.34 (m, 1H), 4.02-3.94 (m, 1H), 3.48-3.39 (m, 1H), 2.54-2.35 (m, 5H), 2.01-1.91 (m, 1H), 1.76-1.72 (m, 4H), 0.79-0.77 (m, 3H), 0.72-0.66 (m, 3H).

Provenance & Evidence