Reaction Steps
Trimethylsilyltrifluoromethanesulfonate (193 μL, 1.07 mmol) was added dropwise 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 but-3-enyl ester (438 mg, 0.59 mmol) in dichloromethane (10 mL) at 0° C. under nitrogen and the reaction was stirred for 60 minutes. To this was added N,N-diisopropylethylamine (412 μL, 2.37 mmol) and the reaction was warmed to room temperature. The volatiles were evaporated to afford a colourless foam which dissolved in acetonitrile (10 mL). 1-Hydroxybenzotriazole (100 mg, 0.59 mmol) was added, followed by N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (136 mg, 0.71 mmol) and (E)-(2R,3R,4S,5S)-3,5-dimethoxy-2,4-dimethyl-nona-6,8-dienoic acid (144 mg, 0.59 mmol) and the reaction was stirred at room temperature for 18 h. The solvent was evaporated and the residue was suspended in ethyl acetate. This was washed with saturated ammonium chloride, saturated sodium bicarbonate, dried over anhydrous sodium sulfate and the solvent evaporated. The residue was purified by eluting through a plug of silica gel (eluting with ethyl acetate) to afford the title compound as a yellow oil (326 mg, 64%). 1H NMR (300 MHz, CDCl3) δ0.18 (s, 6H), 0.75 (d, J=6.9 Hz, 2H), 0.98 (s, 9H), 1.02 (d, J=6.9 Hz, 2H), 1.36-1.50 (m, 3H), 1.65-1.86 (m, 3H), 2.27-2.36 (m, 1H), 2.42 (app q, J=6.7 Hz, 2H), 2.60-3.00 (m, 4H), 3.13 (dd, J=6.2, 13.4 Hz, 1H), 3.25 (s, 3H), 3.33 (s, 3H), 3.37-3.52 (m, 2H), 3.80 (s, 3H), 3.78-3.85 (m, 1H), 4.11-4.23 (m, 2H), 4.27-4.37 (m, 1H), 4.63 (app q, J=6.0 Hz, 1H), 5.09-5.30 (m, 4H), 5.46 (dd, J=8.7, 15.4 Hz, 1H), 5.54-5.64 (m, 1H), 5.71-5.86 (m, 1H), 6.17-6.48 (m, 4H), 6.60-6.64 (m, 1H), 6.68 (dd, J=1.6, 8.2 Hz, 1H), 6.74 (d, J=7.6 Hz, 1H), 6.83 (d, J=8.5 Hz, 2H), 7.10 (t, J=7.8 Hz, 1H), 7.18 (d, J=8.5 Hz, 1H).
