HCID 59269826, compound → HCID 59269825, compound

Participants

Reaction Steps

A solution of (2S,4R)-methyl 4-(allylthio)-4-(biphenyl-4-yl)-1-((S)-2-(tert-butoxycarbonylamino)non-8-enoyl)pyrrolidine-2-carboxylate (123 mg, 0.203 mmol) in Dichloromethane (50 mL) was purged with nitrogen for 30 min. And then Hoveyda-Grubbs Catalyst 2nd Generation (153 mg, 0.243 mmol) was added. The resulting green solution was heated to reflux for 5 h. The reaction was quenched with 2-Mercaptonicotinic acid (62.9 mg, 0.405 mmol) and washed with sat. Na2CO3, and brine. Dried over MgSO4, filtered, concentrated in vacuo. The brown residue was purified by Biotage column, eluted with gradient 5%˜40% EtOAc-Hexane to afford the desired product (3S,13R,15S,E)-methyl 13-(biphenyl-4-yl)-3-(tert-butoxycarbonylamino)-2-oxo-12-thia-1-azabicyclo[11.2.1]hexadec-9-ene-15-carboxylate (93 mg, 0.145 mmol, 71.3% yield) as an off-white solid. NMR analysis showed the configuration of the double bond is exclusively trans. 1H NMR (500 MHz, MeOD) δ ppm 1.39-1.55 (m, 13 H), 1.55-1.75 (m, 4 H), 1.81-1.92 (m, 1 H), 1.97-2.08 (m, 1 H), 2.20-2.31 (m, 1 H), 2.57 (dd, J=12.82, 7.93 Hz, 1 H), 2.76-2.85 (m, 1 H), 2.92 (dd, J=15.87, 7.93 Hz, 1 H, 3.68-3.80 (m, 3 H), 4.20 (t, J=7.78 Hz, 1 H), 4.31-4.40 (m, 1 H), 4.52-4.65 (m, 2 H), 5.65 (dd, J=14.19, 6.87 Hz, 1 H), 5.85 (dd, J=14.95, 7.32 Hz, 1 H), 7.36 (t, J=7.32 Hz, 1 H), 7.41-7.50 (m, 2 H), 7.58-7.74 (m, 6 H). LC-MS (retention time: 3.42 min, method C), MS m/z 579 (M+H).

Provenance & Evidence