2,2,2-Trifluoroethanol → HCID 66833672, compound

Participants

Reaction Steps

A solution of benzyl 4-pent-4-enoylpiperidine-1-carboxylate (10.0 g, 33.2 mmol) and ammonium acetate (6.16 g, 80 mmol) in 2,2,2-trifluoroethanol (10 mL) was treated with tert-butyl isocyanide (2.57 g, 3.50 mL, 31 mmol). After stirring at room temperature for 14 days, the reaction mixture was added to a separatory funnel, diluted with water (100 mL) and extracted with ethyl acetate (2×100 mL). The organic layer was washed with saturated aqueous sodium chloride, dried over MgSO4, filtered and concentrated. MPLC purification (100 g column, 50-100% ethyl acetate in heptane) gave benzyl 4-(2-acetamido-1-(tert-butylamino)-1-oxohex-5-en-2-yl)piperidine-1-carboxylate as colorless oil (8.2 g, 56%). 1H NMR (CDCl3, 300 MHz) δ 7.36-7.31 (m, 5H), 6.98 (bs, 1H), 5.85-5.71 (m, 1H), 5.49 (bs, 1H), 5.11 (s, 2H), 5.00 (dd, J1=16.8 Hz, J2=1.5 Hz, 1H), 4.95 (dd, J1=9.9 Hz, J2=1.5 Hz, 1H), 4.36-4.12 (m, 2H), 2.96 (ddd, J1=14.1 Hz, J2=11.7 Hz, J3=5.4 Hz, 1H), 2.78-2.61 (m, 2H), 2.37 (ddd, J1=12.0 Hz, J2=11.7 Hz, J3=0.9 Hz, 1H), 2.10-1.96 (m, 1H), 2.00 (s, 3H), 1.84-1.64 (m, 3H), 1.56-1.39 (m, 1H), 1.39-1.21 (m, 1H), 1.34 (s, 9H), 1.20-1.03 (m, 1H). ESI MS found for C25H37N3O4 m/z [444.3 (M+1), 466.1 (M+23)].

Provenance & Evidence