Ethanol → HCID 67490881, compound

HRID 1917429Notes

Reaction equation

HRID 1917429 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@:9]12[CH2:16][CH2:15][CH2:14][C@:13]1([Cl: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].O.CCO.C(N(CC)CC)C>C1COCC1>[C:1]([O:5][C:6]([NH:8][C@@:9]12[CH2:16][CH2:15][CH2:14][C@@:13]1([Cl: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

6

Reactant 4

HCID 702EthanolHCID 962WaterHCID 8471TriethylamineHCID 67490758HCID 67490758, compound

Product 1

HCID 67490881HCID 67490881, compoundYield 32.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent4×

Conditions

Temperature
50 °C

Procedure

Under nitrogen atmosphere, to a solution of (1R,5R)-1-(tert-butoxycarbonylamino)-5-chloro-4-oxo-3-[(1R)-1-phenylethyl]-3-azabicyclo[3.3.0]octane (217 mg, 0.573 mmol) in THF (10 mL) was added 1.0M borane-THF complex in THF solution (1.72 mL, 1.72 mmol) at room temperature. After stirring for 14 hours, 1.0M borane-THF complex in THF solution (0.86 mL, 0.86 mmol) was added. The mixture was warmed to 50° C., and stirred for 18 hours. To the mixture was further added 1.0M borane-THF complex in THF solution (0.86 mL, 0.86 mmol) and the mixture was stirred for 24 hours at 50° C. After being cooled to 0° C., to the mixture were added water (1 mL), EtOH (9 mL) and triethylamine (1 mL). The mixture was warmed to 80° C., and stirred for 2 hours. The solvent was distilled off under reduced pressure. To the residue were added saturated aqueous solution of ammonium chloride and ethyl acetate. The separated organic layer was washed with water and brine. The solution was dried over anhydrous sodium sulfate and the solvent was distilled off under reduced pressure. The residue was purified by silica gel flush column chromatography (10% ethyl acetate/hexane) to afford 67.3 mg of the title compound as a colorless oil.

Workup

  1. stirringstirred for 18 hours
  2. stirringthe mixture was stirred for 24 hours at 50° C
  3. temperatureAfter being cooled to 0° C., to the mixture
  4. temperatureThe mixture was warmed to 80° C.
  5. stirringstirred for 2 hours
  6. distillationThe solvent was distilled off under reduced pressure
  7. additionTo the residue were added saturated aqueous solution of ammonium chloride and ethyl acetate
  8. washThe separated organic layer was washed with water and brine
  9. dry with materialThe solution was dried over anhydrous sodium sulfate
  10. distillationthe solvent was distilled off under reduced pressure
  11. customThe residue was purified by silica gel
  12. customflush column chromatography (10% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-a7bc2adcc01e40fca38aed35884d98e5
Source dataset
uspto-grants-2013_12
Patent number
US08618094B2

Reaction notes

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