Acetanilide → 1,1-Difluoro-2,2-dimethyl-3-[3-(N-phenyl-N-acetylamino)-4-fluorobenzyloxy]propane

HRID 414503

Reaction equation

HRID 414503 reaction equation
[F:1][CH:2]([F:17])[C:3]([CH3:16])([CH3:15])[CH2:4][O:5][CH2:6][C:7]1[CH:12]=[CH:11][C:10]([F:13])=[C:9](Br)[CH:8]=1.[C:18]([NH:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)(=[O:20])[CH3:19].C(=O)([O-])[O-].[K+].[K+].COCCOCCN(CCOCCOC)CCOCCOC>C(OCC)(=O)C.CN(C)C=O>[F:1][CH:2]([F:17])[C:3]([CH3:16])([CH3:15])[CH2:4][O:5][CH2:6][C:7]1[CH:12]=[CH:11][C:10]([F:13])=[C:9]([N:21]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:18](=[O:20])[CH3:19])[CH:8]=1

Participants

7

Reactant 4

HCID 904AcetanilideHCID 11430Potassium CarbonateHCID 112414Ethanamine, 2-(2-methoxyethoxy)-N,N-bis[2-(2-methoxyethoxy)ethyl]-HCID 212810781,1-Difluoro-2,2-dimethyl-3-(3-bromo-4-fluorobenzyloxy)propane

Product 1

HCID 212810891,1-Difluoro-2,2-dimethyl-3-[3-(N-phenyl-N-acetylamino)-4-fluorobenzyloxy]propaneYield 38.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 1,1-difluoro-2,2-dimethyl-3-(3-bromo-4-fluorobenzyloxy)propane (1.5 g), acetanilide (0.716 g), cuprous chloride (0.1 g); potassium carbonate (0.67 g), dry N,N-dimethylformamide (10 cm3) and tri[2-(2-methoxyethoxy)ethyl]amine (catalytic quantity) was heated at 158° C. for 4 days under an atmosphere of nitrogen; the mixture was then stood at the ambient temperature for 1 week. The combined organic extracts were washed with water and brine and dried over anhydrous magnesium sulphate. Evaporation of the solvent under reduced pressure gave a dark oil which was subjected to flash column chromatography on a silica gel support, eluting firstly with petroleum ether (boiling range 40°-6° C.) containing 2% by volume ethyl acetate (to give starting materials and a small amount of the deacylated product) and secondly with petroleum ether (boiling range 40°-60° C.) containing 50% by volume ethyl acetate, to give the title compound as a dark oil (0.68 g).

Workup

  1. waitthe mixture was then stood at the ambient temperature for 1 week
  2. washThe combined organic extracts were washed with water and brine
  3. dry with materialdried over anhydrous magnesium sulphate
  4. customEvaporation of the solvent under reduced pressure
  5. customgave a dark oil which
  6. washeluting firstly with petroleum ether (boiling range 40°-6° C.)
  7. additioncontaining 2% by volume ethyl acetate (
  8. customto give

Sources & evidence

ORD record
ord-f709d9e00203454e8dcc3eb8d1b0d612
Source dataset
uspto-grants-1988_12
Patent number
US04792563

Linked notes

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