Water → (1S*,2R*)-5,5-Difluoro-2-[1-(4-methoxybenzyl)-1H-pyrazol-4-yl]cyclohexanol

HRID 337962Notes

Reaction equation

HRID 337962 reaction equation
[F:1][C:2]1([F:14])[CH2:7][C@H:6]([OH:8])[C@@H:5]([C:9]2[CH:10]=[N:11][NH:12][CH:13]=2)[CH2:4][CH2:3]1.C(=O)([O-])[O-].[K+].[K+].[CH3:21][O:22][C:23]1[CH:30]=[CH:29][C:26]([CH2:27]Cl)=[CH:25][CH:24]=1.O>C(#N)C>[F:14][C:2]1([F:1])[CH2:7][C@H:6]([OH:8])[C@@H:5]([C:9]2[CH:13]=[N:12][N:11]([CH2:27][C:26]3[CH:29]=[CH:30][C:23]([O:22][CH3:21])=[CH:24][CH:25]=3)[CH:10]=2)[CH2:4][CH2:3]1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 699934-Methyloxybenzyl chlorideHCID 89962756(1S*,2R*)-5,5-difluoro-2-(1H-pyrazol-4-yl)cyclohexanol

Product 1

HCID 89963182(1S*,2R*)-5,5-Difluoro-2-[1-(4-methoxybenzyl)-1H-pyrazol-4-yl]cyclohexanolYield 25%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of the (1S*,2R*)-5,5-difluoro-2-(1H-pyrazol-4-yl)cyclohexanol (0.24 g, 1.17 mmol) prepared in Example 143c, potassium carbonate (0.32 g, 2.34 mmol) and 4-methoxybenzyl chloride (0.16 mL, 1.17 mmol) in acetonitrile (5.9 mL) was stirred at 80° C. for 12 hours. After allowing to cool, water (20 mL) was added to the reaction solution, and an organic layer was extracted with ethyl acetate (20 mL). The thus obtained organic layer was dried over anhydrous sodium sulfate. After vacuum concentration, the residue was purified with silica gel chromatography to yield the title compound (92.9 mg, 25%) as a colorless solid.

Workup

  1. temperatureto cool
  2. extractionan organic layer was extracted with ethyl acetate (20 mL)
  3. dry with materialThe thus obtained organic layer was dried over anhydrous sodium sulfate
  4. concentrationAfter vacuum concentration
  5. customthe residue was purified with silica gel chromatography

Sources & evidence

ORD record
ord-209d459c4190421c9eef00a673f1f7c7
Source dataset
uspto-grants-2014_11
Patent number
US08889741B2

Reaction notes

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