Potassium Carbonate → 2-{3-[(2,2-Difluoro-2-phenylethyl)amino]-6-chloro-2-fluorophenyl}ethanol

HRID 2184192Notes

Reaction equation

HRID 2184192 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=O)[C:10]([F:18])([F:17])[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[C:4]([F:20])[C:3]=1[CH2:21][CH2:22][OH:23].C([O-])([O-])=O.[K+].[K+]>C1COCC1.O>[F:18][C:10]([F:17])([C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)[CH2:9][NH:8][C:5]1[C:4]([F:20])=[C:3]([CH2:21][CH2:22][OH:23])[C:2]([Cl:1])=[CH:7][CH:6]=1

Participants

5

Reactant 2

HCID 11430Potassium CarbonateHCID 22475352N-[4-chloro-2-fluor-3-(2-hydroxyethyl)phenyl]-2,2-difluoro-2-phenylacetamide

Product 1

HCID 224753362-{3-[(2,2-Difluoro-2-phenylethyl)amino]-6-chloro-2-fluorophenyl}ethanolYield 81%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution N-[4-chloro-2-fluor-3-(2-hydroxyethyl)phenyl]-2,2-difluoro-2-phenylacetamide (1.05 g, 3.06 mmol), as prepared according to the procedure in the preceding step, in THF (12 mL) at 0° C. under argon was added a solution of borane-THF complex in THF (12.3 mL, 12.3 mmol, 1.0 M) over a period of 10 minutes, and the reaction mixture continued to stir until the ice-bath expired. The reaction mixture was heated at reflux for 20 hours, and allowed to cool to room temperature. A solution of K2CO3 (1.7 g, 12 mmol) in H2O (12 mL) was added, the THF was removed in vacuo, and the mixture was extracted with DCM (3 times). The extracts were combined, washed with brine, dried over Na2SO4, concentrated, and flash chromatographed on silica gel eluting with EtOAC/DCM (0 and 2.5%) to give the title compound (815 mg, 81% yield) as a colorless oil. 1H-NMR (400 MHz, CDCl3) δ 7.52-7.43 (m, 5H), 6.97 (dd, J=8.8, 1.7 Hz, 1H), 6.51 (t, J=8.9 Hz, 1H), 4.17 (bs, 1H), 3.83 (t, J=6.9 Hz, 2H), 3.74 (dt, J=13.4, 6.6 Hz, 2H), 3.04 (dt, J=6.9, 2.4 Hz, 2H), 1.43 (s, 1H). Mass spectrum (LCMS, ESI) calc'd for C16H16ClF3NO (M+H): 330.1. Found: 330.3.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 20 hours
  3. customthe THF was removed in vacuo
  4. extractionthe mixture was extracted with DCM (3 times)
  5. washwashed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customflash chromatographed on silica gel eluting with EtOAC/DCM (0 and 2.5%)

Sources & evidence

ORD record
ord-7b58971db7654f9a8571a635cb556877
Source dataset
uspto-grants-2005_05
Patent number
US06900231B2

Reaction notes

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