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

HRID 587302

Reaction equation

HRID 587302 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 triflouroacetate (3.67 g, 28.69 mmol) was added dropwise and then 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 organic combinded 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 on 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 organic combinded layers were washed with brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-b1aba7084b0240fa9b3e0da22f79de1d
Source dataset
uspto-grants-2016_01
Patent number
US09226500B2

Linked notes

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