Tetrahydrofuran → HCID 67421212, compound

HRID 2237758Notes

Reaction equation

HRID 2237758 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]1[CH2:14][N:13]([C:15]2[CH:24]=[CH:23][C:18]([C:19]([O:21][CH3:22])=[O:20])=[CH:17][C:16]=2[N+:25]([O-])=O)[C:12](=O)[CH2:11][CH:10]1[C:29]1[CH:34]=[C:33]([F:35])[C:32]([F:36])=[CH:31][C:30]=1[F:37])=[O:7])([CH3:4])([CH3:3])[CH3:2].C1COCC1>O.[Ni]>[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:14][N:13]2[C:12](=[N:25][C:16]3[CH:17]=[C:18]([C:19]([O:21][CH3:22])=[O:20])[CH:23]=[CH:24][C:15]=32)[CH2:11][C@@H:10]1[C:29]1[CH:34]=[C:33]([F:35])[C:32]([F:36])=[CH:31][C:30]=1[F:37])=[O:7])([CH3:3])([CH3:2])[CH3:4]

Participants

5

Reactant 2

HCID 8028TetrahydrofuranHCID 67418782HCID 67418782, compound

Product 1

HCID 67421212HCID 67421212, compound

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 962WaterSolvent

Procedure

To the product of Step A was added 15 mL of THF, and 2 mL of a slurry of Raney 2800 nickel in water. The mixture was then stirred under hydrogen (1 atm) for 1 h, filtered trough a pad of Celite and the filter cake washed with 50 mL of methanol and 25 mL of methylene chloride. The solution was concentrated in vacuo, the product dissolved in 15 mL of a 13:1 solution mixture of toluene/acetic acid and the mixture heated to reflux for 2 h. After cooling to ambient temperature, the mixture was concentrated in vacuo and the product purified directly by reverse phase HPLC (YMC Pro-C18 column, gradient elution, 5% to 80% acetonitrile/water with 0.1% TFA) to afford the title compound as a white foam. LC/MS 476.4 (M+1).

Workup

  1. filtrationfiltered trough a pad of Celite
  2. washthe filter cake washed with 50 mL of methanol and 25 mL of methylene chloride
  3. concentrationThe solution was concentrated in vacuo
  4. dissolutionthe product dissolved in 15 mL of a 13:1 solution mixture of toluene/acetic acid
  5. temperaturethe mixture heated
  6. temperatureto reflux for 2 h
  7. concentrationthe mixture was concentrated in vacuo
  8. customthe product purified directly by reverse phase HPLC (YMC Pro-C18 column, gradient elution, 5% to 80% acetonitrile/water with 0.1% TFA)

Sources & evidence

ORD record
ord-e5b2c10c1ba948b4946c06902e3d2083
Source dataset
uspto-grants-2010_05
Patent number
US07718667B2

Reaction notes

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