Diisopropylethylamine → HCID 68408480, compound

Participants

Reaction Steps

A suspension of 4-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)benzoic acid (INTERMEDIATE 2, 67 mg, 0.219 mmol), o-benzotriazol-1-yl-tetramethyluronium hexafluorophosphate (166 mg, 0.438 mmol), 1-hydroxybenzotriazole hydrate (50 mg, 0.327 mmol), and diisopropylethylamine (0.2 ml, 1.145 mmol) in dichloromethane (1 ml) was stirred for 5 min at room temperature, and then a solution of (4R,5R)-5-(aminomethyl)-4-(3,4-difluorophenyl)-1,3-oxazolidin-2-one in dichloromethane (1 ml) was added. The mixture was stirred overnight at 25° C. The mixture was diluted with 10 ml of saturated sodium bicarbonate solution and 10 ml of dichloromethane. The phases were separated and the aqueous phase was extracted with 2×10 ml of dichloromethane. The combined organics were washed with 10 ml of brine, dried (sodium sulfate), and concentrated. The residue was purified by flash chromatography on a Biotage Horizon, 25M column, eluting with 1 column volume of 100% dichloromethane followed by a gradient of 0 to 100% ethyl acetate in dichloromethane over 10 column volumes, to provide the title compound (51 mg, 0.099 mmol, 45.1% yield). Mass spectrum (ESI) 517.2 (M+2). 1H NMR (500 MHz, CDCl3): δ 8.36 (d, J=8.5 Hz, 2H), 8.05 (d, J=8.5 Hz, 2H), 7.95 (s, 1H), 7.52 (s, 1H), 7.35 (m, 1H), 7.23 (m, 2H), 6.02 (s, 1H), 4.79 (d, J=7.5 Hz, 1H), 4.48 (m, 1H), 3.05 (m, 1H), 3.83 (m, 1H), 3.49 (m, 2H), 1.47 (d, J=7.0 Hz, 6H).

Provenance & Evidence