Ammonium Chloride → (1S)-1-(3'-amino-5'-fluorobiphenyl-4-yl)-2,2-difluoroethanol

HRID 530398Notes

Reaction equation

HRID 530398 reaction equation
[Cl-].[NH4+].[F:3][CH:4]([F:23])[C@H:5]([C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[C:17]([N+:19]([O-])=O)[CH:16]=[C:15]([F:22])[CH:14]=2)=[CH:9][CH:8]=1)[OH:6]>C(O)C.O.[Fe]>[NH2:19][C:17]1[CH:18]=[C:13]([C:10]2[CH:9]=[CH:8][C:7]([C@H:5]([OH:6])[CH:4]([F:23])[F:3])=[CH:12][CH:11]=2)[CH:14]=[C:15]([F:22])[CH:16]=1

Participants

6

Reactant 2

HCID 25517Ammonium ChlorideHCID 118307555(1S)-2,2-difluoro-1-(3'-fluoro-5'-nitrobiphenyl-4-yl)ethanol

Product 1

HCID 118307581(1S)-1-(3'-amino-5'-fluorobiphenyl-4-yl)-2,2-difluoroethanol

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Procedure

Ammonium chloride (24.2 mg, 0.453 mmol) was added to a mixture of (1S)-2,2-difluoro-1-(3′-fluoro-5′-nitrobiphenyl-4-yl)ethanol (269 mg, 0.905 mmol) and iron (253 mg, 4.53 mmol) in ethanol (6 mL) and water (3 mL). The mixture was heated to reflux for 1.5 hours. Upon cooling to room temperature, the reaction mixture was filtered through CELITE and washed with ethyl acetate. The filtrate was washed with saturated aqueous NaHCO3 and brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography (ethyl acetate/hexanes) to yield (1S)-1-(3′-amino-5′-fluorobiphenyl-4-yl)-2,2-difluoroethanol. MS ESI calc'd. for C14H13F3NO [M+H]+ 268, found 268.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 1.5 hours
  3. filtrationthe reaction mixture was filtered through CELITE
  4. washwashed with ethyl acetate
  5. washThe filtrate was washed with saturated aqueous NaHCO3 and brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by silica gel chromatography (ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-fe93345046f34613878d74a6cf765aee
Source dataset
uspto-grants-2016_05
Patent number
US09353066B2

Reaction notes

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