Water → 3-[3-Chloro-4-(difluoromethoxy)phenyl]-1-cyclopentylpropan-1-one

HRID 858757Notes

Reaction equation

HRID 858757 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][CH2:10][C:11]([CH:13]2[CH2:17][CH2:16][CH2:15][CH2:14]2)=[O:12])[CH:5]=[CH:6][C:7]=1[OH:8].Cl[C:19]([F:25])([F:24])C(OC)=O.C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][CH2:10][C:11]([CH:13]2[CH2:17][CH2:16][CH2:15][CH2:14]2)=[O:12])[CH:5]=[CH:6][C:7]=1[O:8][CH:19]([F:25])[F:24]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 73935Methyl chlorodifluoroacetateHCID 587626963-(3-Chloro-4-hydroxyphenyl)-1-cyclopentylpropan-1-one

Product 1

HCID 587625533-[3-Chloro-4-(difluoromethoxy)phenyl]-1-cyclopentylpropan-1-oneYield 85.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 3-(3-chloro-4-hydroxyphenyl)-1-cyclopentylpropan-1-one (15 g, 59.35 mmol, Example B(58), Step 2)), methyl 2-chloro-2,2-difluoroacetate (17.15 g, 118.7 mmol, 2 equiv) and K2CO3 (12.4 g, 124.6 mmol, 2.1 equiv) in dry DMF (150 mL) was stirred at 75–80° C. for 2 h. The mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with aqueous 1 M NaOH and brine. The organic phase was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was subjected to fractional distillation affording 15.3 g (72%) of material that was about 80% pure by 1H NMR (bp 70° C./2 Torr).

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic layer was washed with aqueous 1 M NaOH and brine
  3. dry with materialThe organic phase was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. distillationThe residue was subjected to fractional distillation

Sources & evidence

ORD record
ord-b3951b387bd14e4cab3eea4574d15c9d
Source dataset
uspto-grants-2006_12
Patent number
US07148226B2

Reaction notes

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