HCID 67491001, compound → HCID 67491116, compound

HRID 1917339Notes

Reaction equation

HRID 1917339 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@:9]12[CH2:16][CH2:15][CH2:14][C@:13]1([F:17])[C:12](=O)[N:11]([C@@H:19]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[CH3:20])[CH2:10]2)=[O:7])([CH3:4])([CH3:3])[CH3:2]>O1CCCC1>[C:1]([O:5][C:6]([NH:8][C@@:9]12[CH2:16][CH2:15][CH2:14][C@:13]1([F:17])[CH2:12][N:11]([C@@H:19]([C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)[CH3:20])[CH2:10]2)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

3

Reactant 1

HCID 67491001HCID 67491001, compound

Product 1

HCID 67491116HCID 67491116, compoundYield 93.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

(1R,5R)-1-(tert-Butoxycarbonylamino)-5-fluoro-4-oxo-3-[(1R)-1-phenylethyl]-3-azabicyclo[3.3.0]octane (3.69 g, 10.2 mmol) was dissolved in tetrahydrofuran (200 mL). A 1.20 M solution of a borane-tetrahydrofuran complex in tetrahydrofuran (42.4 mL, 50.9 mmol) was added dropwise under ice-cooling, and the mixture was stirred for two hours while gradually heating to room temperature. The solvent was evaporated under reduced pressure. Under ice-cooling, 90% aqueous ethanol (100 mL) and triethylamine (100 mL) were added to the residue, and the mixture was heated to reflux for two hours. The solvent was evaporated under reduced pressure, and then the residue was extracted with saturated sodium bicarbonate water and dichloromethane. Thereafter, the target substance was extracted from the aqueous layer with dichloromethane. The organic layers were combined, washed with brine, and dried over anhydrous sodium sulfate. After filtration, the solvent was evaporated under reduced pressure, and the resulting residue was subjected to silica gel column chromatography (hexane:ethyl acetate=95:5→90:10) to give 3.33 g of the title compound as a pale yellow oil.

Workup

  1. temperaturecooling
  2. customThe solvent was evaporated under reduced pressure
  3. temperatureUnder ice-cooling
  4. addition90% aqueous ethanol (100 mL) and triethylamine (100 mL) were added to the residue
  5. temperaturethe mixture was heated
  6. temperatureto reflux for two hours
  7. customThe solvent was evaporated under reduced pressure
  8. extractionthe residue was extracted with saturated sodium bicarbonate water and dichloromethane
  9. extractionThereafter, the target substance was extracted from the aqueous layer with dichloromethane
  10. washwashed with brine
  11. dry with materialdried over anhydrous sodium sulfate
  12. filtrationAfter filtration
  13. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-919d22163757407ca9e520aa4750fefc
Source dataset
uspto-grants-2013_12
Patent number
US08618094B2

Reaction notes

Loading…