Hydrochloric Acid → 2-[(3-Bromo-5-chlorophenyl)oxy]-1-chloro-3-fluoro-4-methylbenzene

HRID 1874936Notes

Reaction equation

HRID 1874936 reaction equation
N(OC(C)(C)C)=O.[Br:8][C:9]1[CH:10]=[C:11]([O:16][C:17]2[C:22]([F:23])=[C:21]([CH3:24])[CH:20]=[CH:19][C:18]=2N)[CH:12]=[C:13]([Cl:15])[CH:14]=1.[ClH:26].CCOC(C)=O>C(#N)C>[Br:8][C:9]1[CH:10]=[C:11]([O:16][C:17]2[C:22]([F:23])=[C:21]([CH3:24])[CH:20]=[CH:19][C:18]=2[Cl:26])[CH:12]=[C:13]([Cl:15])[CH:14]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 10906Tert-Butyl nitriteHCID 68487875HCID 68487875, compound

Product 1

HCID 684866152-[(3-Bromo-5-chlorophenyl)oxy]-1-chloro-3-fluoro-4-methylbenzeneYield 60%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To an oven dried flask was added CuCl2 (4.06 g, 30.2 mmol). The flask was placed under high vacuum, flushed with nitrogen and acetonitrile (30 mL) was added. t-Butyl nitrite (4.50 mL, 37.8 mmol) was added dropwise. The stirred solution was placed in an oil bath at 50° C. under gentle stream of nitrogen, heated for 5 min and a solution of {2-[(3-bromo-5-chlorophenyl)oxy]-3-fluoro-4-methylphenyl}amine in acetonitrile (40 mL) was added dropwise. The reaction was stirred for 0.5 h, cooled in an ice bath and poured into ice cold, aqueous HCl (1 N, 125 mL). EtOAc (100 mL) was added and the layers were separated. The aqueous layer was extracted with EtOAc (2×100 mL). The organic extracts were combined, dried over Na2SO4, filtered and evaporated. The crude material was purified by column chromatography (0% to 25% EtOAc/hexanes gradient) to afford the title compound (3.2 g, 60%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ ppm 7.48-7.47 m, 1H), 7.41-7.38 (m, 1H), 7.32-7.28 (m, 1H), 7.11-7.10 (m, 1H), 7.04-7.03 (m, 1H), 2.27 (s, 3H).

Workup

  1. customTo an oven dried flask
  2. customflushed with nitrogen and acetonitrile (30 mL)
  3. additionwas added
  4. customThe stirred solution was placed in an oil bath at 50° C. under gentle stream of nitrogen
  5. temperatureheated for 5 min
  6. temperaturecooled in an ice bath
  7. customthe layers were separated
  8. extractionThe aqueous layer was extracted with EtOAc (2×100 mL)
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. customevaporated
  12. customThe crude material was purified by column chromatography (0% to 25% EtOAc/hexanes gradient)

Sources & evidence

ORD record
ord-18509c9fa6494e02bb260e2ef3d3ebd5
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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