tert-butyl N-[(3aS,6aR)-6,6-difluoro-1,2,3,4,5,6a-hexahydrocyclopenta[c]pyrrol-3a-yl]carbamate

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of (1S,5R)-1-tert-butoxycarbonylamino-6,6-difluoro-3-azabicyclo[3.3.0]octane (318 mg, 1.21 mmol), ethyl 7-bromo-6-fluoro-1-[(1R,2S)-2-fluorocyclopropyl]-1,4-dihydro-8-methyl-4-oxoquinoline-3-carboxylate (426 mg, 1.10 mmol), 1,1′-bis(diphenylphosphino)ferrocene (183 mg, 0.331 mmol), tris(dibenzylideneacetone)dipalladium(0) (101 mg, 0.110 mmol) and cesium carbonate (718 mg, 2.20 mmol) in dioxane (5.51 mL) was stirred at room temperature for 30 minutes, and at 100° C. for 11 hours under argon atmosphere. The mixture was diluted with water, and extracted with ethyl acetate and chloroform (3×). The combined organic layer was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel flush column chromatography (ethyl acetate/hexane=10:90→50:50→67:33→ethyl acetate) to afford 436 mg of the title compound as a pale yellow foam. at 100° C. for 11 hours under argon atmosphere extracted with ethyl acetate and chloroform (3×) The combined organic layer was dried over anhydrous sodium sulfate the solvent was distilled off under reduced pressure The residue was purified by silica gel flush column chromatography (ethyl acetate/hexane=10:90→50:50→67:33→ethyl acetate)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: [(1S,5R)-1-tert-Butoxycarbonylamino-6,6-difluoro-3-azabicyclo[3,3,0]octan-3-yl]carboxylic acid benzyl ester (65.0 mg, 0.16 mmol) was dissolved in methanol (10 mL). 10% palladium-carbon (50% wet) (20 mg) was added, and the mixture was stirred in a hydrogen atmosphere for one hour. The catalyst was removed by filtration, and then the filtrate was concentrated under reduced pressure. A 1N sodium hydroxide solution was added, followed by extraction with chloroform. After drying over anhydrous sodium sulfate and filtration, the filtrate was concentrated under reduced pressure to give 43 mg of the title compound as a colorless solid. The catalyst was removed by filtration the filtrate was concentrated under reduced pressure A 1N sodium hydroxide solution was added followed by extraction with chloroform After drying over anhydrous sodium sulfate and filtration the filtrate was concentrated under reduced pressure