Dimethyl Sulfoxide → 1-(1-Fluorocyclopropyl)-3-(4-fluorophenyl)-3-methylbutan-1-one

HRID 400627Notes

Reaction equation

HRID 400627 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[F:11][C:12]1([CH:15]([OH:27])[CH2:16][C:17]([C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=2)([CH3:19])[CH3:18])[CH2:14][CH2:13]1.C(N(CC)CC)C>ClCCl>[F:11][C:12]1([C:15](=[O:27])[CH2:16][C:17]([C:20]2[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=2)([CH3:19])[CH3:18])[CH2:13][CH2:14]1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 60026890HCID 60026890, compound

Product 1

HCID 600264051-(1-Fluorocyclopropyl)-3-(4-fluorophenyl)-3-methylbutan-1-oneYield 51.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent4×

Procedure

2.2 mL of a 2 M solution of oxalyl chloride in dichloromethane was diluted with 2.5 mL of dichloromethane and cooled on dry ice/acetone bath. To this solution was added a dropwise a solution of 0.7 mL of DMSO in 2.5 mL of dichloromethane. After 10 minutes, a solution of the above crude 1-(1-fluorocyclopropyl)-3-(4-fluorophenyl)-3-methylbutan-1-ol (0.72 g, 3.0 mmol) in 2 mL of dichloromethane was added and the mixture was stirred for 15 minutes. 4 mL of triethylamine was added, the cooling bath was removed, the mixture was allowed to warm to room temperature and was then quenched with water and diluted with hexanes. The organic layer was separated, washed with water, dried, filtered, and concentrated in vacuo. The residue was purified by chromatography over silica gel (eluent: hexanes to hexanes-dichloromethane (4:1) gradient) to give 0.37 g of the title product as an oil.

Workup

  1. temperaturecooled on dry ice/acetone bath
  2. customthe cooling bath was removed
  3. customwas then quenched with water
  4. additiondiluted with hexanes
  5. customThe organic layer was separated
  6. washwashed with water
  7. customdried
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by chromatography over silica gel (eluent: hexanes to hexanes-dichloromethane (4:1) gradient)

Sources & evidence

ORD record
ord-6c567cbf35c845408f640f6c69bc66c6
Source dataset
uspto-grants-2014_06
Patent number
US08741897B2

Reaction notes

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