2,2-Difluorocyclopropyl(4-chlorophenyl) ketone → 1-(4-Chlorophenyl)-1-(2,2-difluorocyclopropyl)ethanol

HRID 561458Notes

Reaction equation

HRID 561458 reaction equation
[CH3:1][Mg]Br.[Cl:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]([CH:13]2[CH2:15][C:14]2([F:17])[F:16])=[O:12])=[CH:7][CH:6]=1>C(OCC)C>[Cl:4][C:5]1[CH:6]=[CH:7][C:8]([C:11]([CH:13]2[CH2:15][C:14]2([F:16])[F:17])([OH:12])[CH3:1])=[CH:9][CH:10]=1

Participants

4

Reactant 2

HCID 248658712,2-Difluorocyclopropyl(4-chlorophenyl) ketoneHCID 178418573HCID 178418573, compound

Product 1

HCID 583922561-(4-Chlorophenyl)-1-(2,2-difluorocyclopropyl)ethanol

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

5.7 ml (17.1 mmol) of a 3N solution of methylmagnesium bromide in diethyl ether were added to 2.47 g (11.4 mmol) of the compound from Example 124A in 40 ml of diethyl ether at RT, and the mixture was stirred at RT overnight. The reaction mixture was added to a saturated, ice-cold aqueous ammonium chloride solution, the phases were separated, the aqueous phase was extracted with dichloromethane, and the combined organic phases were dried over magnesium sulfate, filtered and concentrated. The residue was purified by flash chromatography on silica gel (mobile phase: toluene/ethyl acetate gradient) to result in 2.09 g (78% of theory) of a mixture of the diastereomers of the title compound.

Workup

  1. additionThe reaction mixture was added to a saturated, ice-cold aqueous ammonium chloride solution
  2. customthe phases were separated
  3. extractionthe aqueous phase was extracted with dichloromethane
  4. dry with materialthe combined organic phases were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography on silica gel (mobile phase: toluene/ethyl acetate gradient)

Sources & evidence

ORD record
ord-e45977603075426dacc7046eda30898d
Source dataset
uspto-grants-2011_11
Patent number
US08063234B2

Reaction notes

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