Sodium hydride → (S)-1-{(S)-2-[(S)-2-tert-Butoxycarbonylamino-3-(4-methoxy-phenyl)-propionylamino]-3-[3-(tert-butyl-dimethyl-silanyloxy)-phenyl]-propionyl}-hexahydro-pyridazine-3-carboxylic acid but-3-enyl ester

Participants

Reaction Conditions

Reaction Steps

Sodium hydride (6 mg, 0.139 mmol) was added to a solution of (S)-1-{(S)-2-[(S)-2-tert-butoxycarbonylamino-3-(4-methoxy-phenyl)-propionylamino]-3-[3-(tert-butyl-dimethyl-silanyloxy)-phenyl]-propionyl}-hexahydro-pyridazine-3-carboxylic acid 2,2,2-trichloro-ethyl ester (570 mg, 0.698 mmol) and 3-buten-1-ol (601 μL, 6.98 mmol) in tetrahydrofuran (10 mL) and the reaction stirred at 50° C. under nitrogen for 18 h. The reaction was cooled and the mixture passed through a plug of silica gel (eluting twice with ethyl acetate, 50 mL) to afford the title compound (438 mg, 85%) as a colourless oil (438 mg, 85%). 1H NMR (300 MHz, CDCl3) δ0.20 (s, 6H), 1.00 (s, 9H), 1.10-140 (m, 2H), 1.40 (s, 9H), 1.72-1.86 (m, 2H), 2.33-2.46 (m, 3H), 2.60-3.05 (m, 5H), 3.50 (d, 11.4 Hz, 1H), 3.80 (s, 3H), 4.15-4.35 (m, 4H), 4.95 (br s, 1H), 5.09-5.19 (m, 2H), 5.60-5.70 (m, 1H), 5.71-5.87 (m, 1H), 6.42 (d, J=8.0 Hz, 1H), 6.62-6.80 (m, 3H), 6.82 (d, J=8.7 Hz, 2H), 7.07-7.16 (m, 3H). LCMS (m/z) 739.40 [M+H], Tr=5.82 min.

Provenance & Evidence