2,2,2-Trifluoroethanol → HCID 66833035, compound

Participants

Reaction Steps

A solution of (R)-1-(1-(2-nitrophenylsulfonyl)pyrrolidin-3-yl)pent-4-en-1-one (1.03 g, 3.04 mmol) and ammonium acetate (0.548 g, 7.11 mmol) in 2,2,2-trifluoroethanol (1.5 mL, 2.0 mmol) was treated with tert-butyl isocyanide (1.5 mL, 24 mmol) followed by stirring at room temperature. After 8 hours, an additional 0.5 mL of isocyanate was added and the temperature of the reaction was increased to 40° C. After stirring overnight at 40° C., the crude reaction was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate. The organic layer was separated, dried over Na2SO4, filtered and concentrated prior to purification of the crude oil by flash column chromatography (silica gel, using 0-100% ethyl acetate in hexanes) to give 2-acetamido-N-tert-butyl-2-((R)-1-(2-nitrophenylsulfonyl)pyrrolidin-3-yl)hex-5-enamide (1.00 g, 68.4%) as a brown foam. 1H NMR (400 MHz, CDCl3, mixture of diastereoisomers) δ 8.07-8.02 (m, 1H), 7.81-7.71 (m, 2H), 7.64-7.59 (m, 1H), 6.85 (2×s, 1H), 5.98-5.63 (br, m, 2H), 5.06-4.95 (m, 2H), 3.61-2.90 (m, 6H), 2.02-2.00 (2×s, 3H), 1.95-1.41 (m, 5H), 1.38-1.36 (2×s, 9H),; ESI MS found for C22H32N4O6S m/z 481.2 (M+H)+; 479.3 (M−H)−.

Provenance & Evidence