Borane;tetrahydrofuran → HCID 18427823, compound

HRID 1279655Notes

Reaction equation

HRID 1279655 reaction equation
[CH2:1]([N:8]1[CH2:12][CH:11]([C:13]2([NH:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][C:15]([F:18])([F:17])[CH2:14]2)[CH2:10][C:9]1=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.B.O1CCCC1>O1CCCC1>[CH2:1]([N:8]1[CH2:9][CH2:10][CH:11]([C:13]2([NH:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:14][C:15]([F:18])([F:17])[CH2:16]2)[CH2:12]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 2723981Borane;tetrahydrofuranHCID 18427827HCID 18427827, compound

Product 1

HCID 18427823HCID 18427823, compoundYield 62.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Under an atmosphere of nitrogen, 825 mg (2.17 mmol) of 1-benzyl-4-[3-(tert-butoxycarbonylamino)-1,1-difluorocyclobutan-3-yl]-2-pyrrolidone (Isomer F2) was dissolved in 20 ml of tetrahydrofuran to which, while cooling in an ice bath with stirring, was subsequently added 6.51 ml of 1 N borane-tetrahydrofuran complex tetrahydrofuran solution. Ten minutes thereafter, the ice bath was detached and the reaction mixture was stirred at room temperature for 18 hours. After evaporation of the solvent under a reduced pressure, the thus obtained residue was mixed with 30 ml of 80% ethanol and 3 ml of triethylamine and heated under reflux for 2 hours. After evaporation of the solvent under a reduced pressure, the thus obtained residue was mixed with ethyl acetate and saturated sodium bicarbonate aqueous solution to effect separation of layers. The organic layer was washed with saturated brine, the aqueous layer was extracted with ethyl acetate and then the organic layers were combined and dried over anhydrous sodium sulfate. After filtration, the solvent was evaporated under a reduced pressure and the resulting residue was purified by a silica gel column chromatography to give 494 mg (62.2%) of the title compound. 1H-NMR data of the thus obtained compound coincided with the aforementioned data of its enantiomer Isomer F1.

Workup

  1. temperaturewhile cooling in an ice bath
  2. customTen minutes
  3. stirringthe reaction mixture was stirred at room temperature for 18 hours
  4. customAfter evaporation of the solvent under a reduced pressure
  5. additionthe thus obtained residue was mixed with 30 ml of 80% ethanol and 3 ml of triethylamine
  6. temperatureheated
  7. temperatureunder reflux for 2 hours
  8. customAfter evaporation of the solvent under a reduced pressure
  9. additionthe thus obtained residue was mixed with ethyl acetate and saturated sodium bicarbonate aqueous solution
  10. customseparation of layers
  11. washThe organic layer was washed with saturated brine
  12. extractionthe aqueous layer was extracted with ethyl acetate
  13. dry with materialdried over anhydrous sodium sulfate
  14. filtrationAfter filtration
  15. customthe solvent was evaporated under a reduced pressure
  16. customthe resulting residue was purified by a silica gel column chromatography

Sources & evidence

ORD record
ord-3d596cd26dd1427198ec0060eb1418f8
Source dataset
uspto-grants-2002_09
Patent number
US06448266B1

Reaction notes

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