Reaction Steps
To a solution of (2R,6S,13aS,14aR,16aS,Z)-ethyl 2-(biphenyl-4-yl)-6-(tert-butoxycarbonylamino)-2-(butylthio)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a-carboxylate (59 mg, 0.082 mmol) in THF (1 mL) and MeOH (1.000 mL) was added pre-made solution of Lithium hydroxide monohydrate (6.90 mg, 0.164 mmol) in water (1 mL). The resulting cloudy solution was stirred at room for 5 h. LC/MS analysis showed partial reaction. Another portion of Lithium hydroxide monohydrate (6.90 mg, 0.164 mmol) in water (0.2 ml) was added and stirred for additional 17 hours. LC/MS analysis showed there was still small portion of starting material remained. Another portion of Lithium hydroxide monohydrate (6.90 mg, 0.164 mmol) in water (0.2 ml) was added and stirred for additional 5 hours. Quenched with 5% citric acid, extracted with ethyl acetate. The organic layer was washed with brine, dried over MgSO4, filtered, and concentrated to afford the desired product (2R,6S,13aS,14aR,16aS,Z)-2-(biphenyl-4-yl)-6-(tert-butoxycarbonylamino)-2-(butylthio)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a-carboxylic acid (57 mg, 0.074 mmol, 90% yield) as a white foam. 1H NMR (500 MHz, MeOD) δ ppm 0.84 (t, J=7.32 Hz, 3 H) 1.14-1.37 (m, 5 H) 1.38-1.54 (m, 16 H) 1.53-1.68 (m, 4 H) 1.82-1.95 (m, 1 H) 1.96-2.12 (m, 1 H) 2.21-2.38 (m, 2 H) 2.42 (dt, J=12.21, 7.17 Hz, 1 H) 2.48-2.63 (m, 1 H) 2.84-3.00 (m, 1 H) 3.92-4.18 (m, 2 H) 4.49 (dd, J=10.38, 2.75 Hz, 1 H) 5.18 (d, J=10.68 Hz, 1 H) 5.35 (t, J=9.77 Hz, 1 H) 5.56-5.68 (m, 1 H) 7.30-7.39 (m, 1 H) 7.45 (t, J=7.63 Hz, 2 H) 7.55-7.63 (m, 4 H) 7.77 (d, J=8.24 Hz, 2 H). LC-MS (retention time: 3.34 min, method C), MS m/z 690(M+H).
