tert-butyl ((2S,3S)-1-((2S,4R)-4-hydroxy-2-(((1R,2S)-1-(((1-methylcyclopropyl)sulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)pyrrolidin-1-yl)-1-oxo-3-(pent-4-en-1-yloxy)pentan-2-yl)carbamate → tert-butyl ((2R,6S,7S,13aS,14aR,16aS,Z)-7-ethyl-2-hydroxy-14a-(((1-methylcyclopropyl)sulfonyl)carbamoyl)-5,16-dioxo-2,3,5,6,7,9,10,11,13a,14,14a,15,16,16a-tetradecahydro-1H-cyclopropa[i]pyrrolo[1,2-e][1,5,8]oxadiazacyclopentadecin-6-yl)carbamate

Participants

Reaction Conditions

Reaction Steps

To a round-bottom flask equipped with a stir bar was added tert-butyl ((2S,3S)-1-((2S,4R)-4-hydroxy-2-(((1R,2S)-1-(((1-methylcyclopropyl)sulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)pyrrolidin-1-yl)-1-oxo-3-(pent-4-en-1-yloxy)pentan-2-yl)carbamate (all material from step 4, 480 mg, 0.749 mmol) and DCE (100 mL). The solution was sparged with nitrogen for 30 minutes. To the solution was added Hoveyda-Grubbs Catalyst 2nd Generation (23 mg, 0.037 mmol). The solution was stirred at 80° C. for 2 h, then was cooled to 45° C. and was stirred for 3 days. The solution was concentrated in vacuo and the resulting residue was subjected to C18 chromatography (water with 0.1% TFA:acetonitrile with 0.1% TFA, 60:40 to 0:100) to afford tert-butyl ((2R,6S,7S,13aS,14aR,16aS,Z)-7-ethyl-2-hydroxy-14a-(((1-methylcyclopropyl)sulfonyl)carbamoyl)-5,16-dioxo-2,3,5,6,7,9,10,11,13a,14,14a,15,16,16a-tetradecahydro-1H-cyclopropa[i]pyrrolo[1,2-e][1,5,8]oxadiazacyclopentadecin-6-yl)carbamate as a brown solid foam (100 mg, 22%). MS: MS m/z 613.4 (M++1).

Provenance & Evidence