Ethanol → HCID 67490841, compound

{(1S,5R,6S)-6-Fluoro-4-oxo-3-[(1R)-1-phenylethyl]-3-azabicyclo[3,3,0]octan-1-yl}carboxylic acid tert-butyl ester (402 mg, 1.16 mmol) was dissolved in tetrahydrofuran (20 mL), and a 1 M borane-tetrahydrofuran complex (5.79 mL, 5.79 mmol) was added dropwise in a nitrogen atmosphere. After two hours, a 1 M borane-tetrahydrofuran complex (3.47 mL, 3.47 mmol) was added; after 14 hours, a 1 M borane-tetrahydrofuran complex (3.47 mL, 3.47 mmol) was further added. After stirring for 2.5 hours, ethanol (18 mL), water (2 mL), and triethylamine (2 mL) were added, and the mixture was stirred at 80° C. for two hours. The reaction solution was evaporated under reduced pressure, and a saturated ammonium chloride solution was added to the resulting residue, followed by extraction with ethyl acetate. The organic layer was washed with water and brine and then dried over anhydrous sodium sulfate. After filtration, the solvent was evaporated under reduced pressure, and the resulting residue was dissolved in dichloromethane (2.8 mL). Benzyloxycarbonyl chloride (1.03 g, 6.04 mmol) was added, and the mixture was stirred at 40° C. for 14 hours. The reaction solution was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (25% ethyl acetate/hexane) to give 359 mg of the title compound as a colorless oil.

1. additiona 1 M borane-tetrahydrofuran complex (5.79 mL, 5.79 mmol) was added dropwise in a nitrogen atmosphere
2. additiona 1 M borane-tetrahydrofuran complex (3.47 mL, 3.47 mmol) was added
3. waitafter 14 hours
4. additiona 1 M borane-tetrahydrofuran complex (3.47 mL, 3.47 mmol) was further added
5. stirringthe mixture was stirred at 80° C. for two hours
6. customThe reaction solution was evaporated under reduced pressure
7. additiona saturated ammonium chloride solution was added to the resulting residue
8. extractionfollowed by extraction with ethyl acetate
9. washThe organic layer was washed with water and brine
10. dry with materialdried over anhydrous sodium sulfate
11. filtrationAfter filtration
12. customthe solvent was evaporated under reduced pressure
13. dissolutionthe resulting residue was dissolved in dichloromethane (2.8 mL)
14. stirringthe mixture was stirred at 40° C. for 14 hours
15. concentrationThe reaction solution was concentrated under reduced pressure
16. customthe residue was purified by silica gel column chromatography (25% ethyl acetate/hexane)

ORD record

ord-02dd150df85a40aa99aba5a955b82d28

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08618094B2