Ethanol → HCID 67490921, compound

HRID 1917306Notes

Reaction equation

HRID 1917306 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@:9]12[CH2:15][CH2:14][C@:13]1([F:16])[C:12](=O)[N:11]([C@@H:18]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[CH3:19])[CH2:10]2)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(O)C.O.C(N(CC)CC)C>O1CCCC1>[C:1]([O:5][C:6]([NH:8][C@@:9]12[CH2:15][CH2:14][C@@:13]1([F:16])[CH2:12][N:11]([C@@H:18]([C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1)[CH3:19])[CH2:10]2)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 702EthanolHCID 962WaterHCID 8471TriethylamineHCID 67490973HCID 67490973, compound

Product 1

HCID 67490921HCID 67490921, compoundYield 68%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A 1.16 M solution of a borane-tetrahydrofuran complex in tetrahydrofuran (6.0 mL) was added dropwise to a solution of (1R,5R)-1-(tert-butoxycarbonylamino)-5-fluoro-4-oxo-3-[(1R)-1-phenylethyl]-3-azabicyclo[3.2.0]heptane (811 mg, 2.33 mmol) in tetrahydrofuran (6.0 mL) at 0° C. over five minutes. The mixture was heated to room temperature, stirred for five hours, and then cooled to −10° C. A mixture of ethanol (9.0 mL)-water (1.0 mL) was carefully added dropwise. After addition of triethylamine (3.0 mL) dropwise, the mixture was heated to reflux for one hour. The reaction solution was concentrated, and the precipitated white solid was removed by filtration through Celite. The filtrate was concentrated, and the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1→4:1) to give 530 mg (68%) of the title compound as a white solid.

Workup

  1. temperaturecooled to −10° C
  2. additionwas carefully added dropwise
  3. temperaturethe mixture was heated
  4. temperatureto reflux for one hour
  5. concentrationThe reaction solution was concentrated
  6. customthe precipitated white solid was removed by filtration through Celite
  7. concentrationThe filtrate was concentrated
  8. customthe resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1→4:1)

Sources & evidence

ORD record
ord-4ee9930e27b54275aba46741486da668
Source dataset
uspto-grants-2013_12
Patent number
US08618094B2

Reaction notes

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