Sodium Hydroxide → Ethyl (2R,6S,12Z,13aS,14aR,16aS)-6-({[(2,2-dimethylpent-4-en-1-yl)oxy]carbonyl}amino)-2-[(6-methoxy-7-vinylisoquinolin-1-yl)oxy]-5,16-dioxo-1,2,3,6,7,8,9,10,11,13a,14,15,16,16a-tetradecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a(5H)-carboxylate

Participants

Reaction Steps

To a stirred solution of 2,2-dimethylpent-4-en-1-ol (66.3 mg, 0.581 mmol) and DIPEA (0.101 mL, 0.581 mmol) in anhydrous 1,4-dioxane (10 mL), at 10° C., under nitrogen, was added a solution of triphosgene (60.3 mg, 0.203 mmol) in 1,4-dioxane (10 mL). The reaction mixture was stirred at RT for 1 hour. The product from Step 6 (178 mg, 0.290 mmol) and 1 M NaOH (0.871 mL) were then added and the reaction mixture was stirred at 50° C. for 15 hours. The reaction mixture was cooled to RT, diluted with aqueous saturated NaHCO3 (20 mL) and extracted with EtOAc (3×30 mL). The combined EtOAc layers were washed with water (30 mL), brine (20 mL), dried over Na2SO4, filtered and concentrated. The residue was chromatographed on silica gel, eluting with 5% to 75% EtOAc in hexane, to give the title product (125 mg). LRMS (ESI) m/z 717.5 [(M+H)+; calcd for C40H53N4O8: 717.4].

Provenance & Evidence