Borane → HCID 57758696, compound

HRID 229542Notes

Reaction equation

HRID 229542 reaction equation
[F:1][CH:2]1[C:6](=O)[N:5]([C@@H:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH3:9])[CH2:4][C@@:3]1([CH3:23])[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17].B>O1CCCC1>[F:1][CH:2]1[CH2:6][N:5]([C@@H:8]([C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH3:9])[CH2:4][C@@:3]1([CH3:23])[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17]

Participants

4

Reactant 2

HCID 6331BoraneHCID 57758650HCID 57758650, compound

Product 1

HCID 57758696HCID 57758696, compoundYield 87%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of tert-butyl(3S)-4-fluoro-3-methyl-5-oxo-1-[(1R)-1-phenylethyl]-pyrrolidine-3-carboxylate (isomer A) (2.58 g, 8.03 mmol) in tetrahydrofuran (50 mL) was added 1.01M solution of borane in tetrahydrofuran (26.2 mL, 26.5 mmol) in an ice bath and the mixture was stirred at room temperature for 15 hours. The reaction mixture was concentrated under reduced pressure, and water (5 mL), ethanol (45 ml), and triethylamine (3 mL) were added in an ice bath, and the mixture was heated under reflux for 1.5 hours. After concentrating the reaction mixture under reduced pressure, water (100 mL) was added, and the mixture was extracted with chloroform (200 mL×2). The organic layer was washed with saturated aqueous solution of sodium chloride (100 mL), and dried with anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the concentrate was purified by silica gel column chromatography (elusion by hexane ethyl acetate, 12:1→2:1) to obtain 2.15 g (87%) of the title compound (isomer A) as a colorless oily substance.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure, and water (5 mL), ethanol (45 ml), and triethylamine (3 mL)
  2. additionwere added in an ice bath
  3. temperaturethe mixture was heated
  4. temperatureunder reflux for 1.5 hours
  5. concentrationAfter concentrating the reaction mixture under reduced pressure, water (100 mL)
  6. additionwas added
  7. extractionthe mixture was extracted with chloroform (200 mL×2)
  8. washThe organic layer was washed with saturated aqueous solution of sodium chloride (100 mL)
  9. dry with materialdried with anhydrous sodium sulfate
  10. filtrationAfter filtration
  11. concentrationthe filtrate was concentrated under reduced pressure
  12. customthe concentrate was purified by silica gel column chromatography (elusion by hexane ethyl acetate, 12:1→2:1)

Sources & evidence

ORD record
ord-da980db9771b490dac87debf6d026591
Source dataset
uspto-grants-2009_07
Patent number
US07563805B2

Reaction notes

Loading…