Hydrochloric Acid → 1-(5-Bromo-2,4-difluorophenyl)ethan-1-one

HRID 1471436Notes

Reaction equation

HRID 1471436 reaction equation
[Al+3].[Cl-].[Cl-].[Cl-].[Br:5][C:6]1[CH:11]=[CH:10][C:9]([F:12])=[CH:8][C:7]=1[F:13].[C:14](Cl)(=[O:16])[CH3:15].Cl>CCOC(C)=O>[Br:5][C:6]1[C:7]([F:13])=[CH:8][C:9]([F:12])=[C:10]([C:14](=[O:16])[CH3:15])[CH:11]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6367Acetyl chlorideHCID 676741-Bromo-2,4-difluorobenzeneHCID 6451240Aluminum(III) Chloride

Product 1

HCID 207853591-(5-Bromo-2,4-difluorophenyl)ethan-1-one

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of AlCl3 (1040 g, 7878.7 mmol) in 1-bromo-2,4-difluorobenzene ([CAS 348-57-2], 600 g, 3108.9 mmol) was stirred for 10 min at 60° C. Acetyl chloride [CAS 75-36-5], 366 g, 4662.4 mmol) was added dropwise in the reaction mixture for 4 h at 60° C. The mixture was stirred an additional 6 h at 95° C. The reaction mixture was cooled to −10° C. Ice (2450 g) was added for 1.5 h. HCl (12 N, 1500 mL) was added and the mixture was stirred for 1 h. EtOAc (9000 mL) was added and the organic layer was washed with water, dried over Na2SO4 and filtered. After concentration, the residue was purified by column chromatography over silica gel (eluent: petroleum ether/EtOAc, 50/1) to yield I-18 (300 g, 41%).

Workup

  1. stirringThe mixture was stirred an additional 6 h at 95° C
  2. temperatureThe reaction mixture was cooled to −10° C
  3. stirringthe mixture was stirred for 1 h
  4. washthe organic layer was washed with water
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationAfter concentration
  8. customthe residue was purified by column chromatography over silica gel (eluent: petroleum ether/EtOAc, 50/1)
  9. customto yield I-18 (300 g, 41%)

Sources & evidence

ORD record
ord-7fdaceea662c407090d79150dfbc0472
Source dataset
uspto-grants-2015_04
Patent number
US09012448B2

Reaction notes

Loading…