Methyl chloroformate → (1S,5R)-5-Benzyloxymethyl-2-oxo-3-[(1R)-1-phenylethyl]-3-azabicyclo[3.2.0]heptane-1-carboxylic acid methyl ester

A 1.0 M solution of lithium hexamethyldisilazide in tetrahydrofuran (14.5 mL, 14.5 mmol) was added to a solution of (4S)-4-benzyloxymethyl-4-(2-bromoethyl)-1-[(1R)-1-phenylethyl]pyrrolidin-2-one (2.75 g, 6.60 mmol) and methyl chloroformate (0.54 mL, 6.93 mmol) in tetrahydrofuran (20 mL) in a nitrogen atmosphere at 0° C. The mixture was stirred for 12 hours while gradually heating to room temperature. The reaction solution was cooled to 0° C. A saturated ammonium chloride solution (5 mL) was added, and the mixture was stirred for 10 minutes. Then, the reaction solution was poured into a mixture of ethyl acetate (100 mL) and water (50 mL), followed by extraction with ethyl acetate (200 mL). The organic layer was washed with brine (50 mL) and then dried over anhydrous sodium sulfate. The drying agent was removed by filtration, and then the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=3:1→2:1→1:1) to give 2.12 g (82%) of the title compound as a pale yellow oil.

1. temperatureThe reaction solution was cooled to 0° C
2. stirringthe mixture was stirred for 10 minutes
3. extractionfollowed by extraction with ethyl acetate (200 mL)
4. washThe organic layer was washed with brine (50 mL)
5. dry with materialdried over anhydrous sodium sulfate
6. customThe drying agent was removed by filtration
7. concentrationthe filtrate was concentrated under reduced pressure
8. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=3:1→2:1→1:1)

ORD record

ord-494535573fec484b8de1597f3052169a

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08618094B2