Hydrochloric Acid → 1-(3,5-Difluoro-4-methoxyphenyl)-2,2,2-trifluoroethanone

HRID 1503795Notes

Reaction equation

HRID 1503795 reaction equation
Br[C:2]1[CH:3]=[C:4]([F:11])[C:5]([O:9][CH3:10])=[C:6]([F:8])[CH:7]=1.[F:12][C:13]([F:19])([F:18])[C:14](OC)=[O:15].Cl>C1COCC1>[F:8][C:6]1[CH:7]=[C:2]([C:14](=[O:15])[C:13]([F:19])([F:18])[F:12])[CH:3]=[C:4]([F:11])[C:5]=1[O:9][CH3:10]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 9893Methyl trifluoroacetateHCID 27732874-Bromo-2,6-difluoroanisole

Product 1

HCID 867225781-(3,5-Difluoro-4-methoxyphenyl)-2,2,2-trifluoroethanoneYield 100.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Isopropyl magnesium chloride lithium chloride complex (22.0 mL, 28.02 mmol) was added dropwise to a stirred solution of 5-bromo-1,3-difluoro-2-methoxybenzene (5.0 g, 22.42 mmol) at −5° C. in THF (100 mL) and the reaction mixture was stirred at same temperature for 30 min. Methyl trifluoroacetate (3.67 g, 28.69 mmol) was added dropwise and the reaction mixture was stirred at ambient temperature for 2 h. A 2 N HCl solution (200 mL) was added to quench the reaction and then it was extracted with diethylether. The combined organic layers were washed with brine, dried (Na2SO4) filtered and concentrated to afford the title compound (5.4 g, crude) as a yellow liquid. The material was taken to next step without further purification. 1H NMR (400 MHz, CDCl3) δ 7.68-7.60 (m, 2H) 4.19 (s, 3H); ESIMS m/z 240.1 ([M]+).

Workup

  1. stirringthe reaction mixture was stirred at ambient temperature for 2 h
  2. customto quench
  3. customthe reaction
  4. extractionit was extracted with diethylether
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-0a3a1ce0e9564545a69564e81aaa8d76
Source dataset
uspto-grants-2015_12
Patent number
US09212164B2

Reaction notes

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