Potassium Carbonate → 4-Bromo-1-chloro-2-[[4-(2,2,2-trifluoroethoxy)phenyl]methyl]benzene

HRID 1055547Notes

Reaction equation

HRID 1055547 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([Cl:16])=[C:6]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=2)[CH:7]=1.C(=O)([O-])[O-].[K+].[K+].[F:23][C:24]([F:38])([F:37])[CH2:25]OS(C1C=CC(C)=CC=1)(=O)=O>CN(C)C=O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([Cl:16])=[C:6]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:25][C:24]([F:38])([F:37])[F:23])=[CH:11][CH:10]=2)[CH:7]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 67942Ethanol, 2,2,2-trifluoro-, 1-(4-methylbenzenesulfonate)HCID 574237514-((5-Bromo-2-chlorophenyl)methyl)phenol

Product 1

HCID 866851464-Bromo-1-chloro-2-[[4-(2,2,2-trifluoroethoxy)phenyl]methyl]benzeneYield 87%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 4-[(5-bromo-2-chloro-phenyl)methyl]phenol 17b (23.4 g, 78.7 mmol) in N,N-dimethylformamide (30 mL) was added potassium carbonate (54.0 g, 394.0 mmol) at room temperature. The mixture was warmed up to 90° C. and stirred for 30 min, and then 2,2,2-trifluoroethyl-p-toluensulfonate (20 g, 78.7 mmol) was added. The reaction mixture was warmed up to 140° C. and stirred for 12 hours. The mixture was cooled to room temperature and filtered. The filtrate was concentrated in vacuo and the residue was partitioned between ethylacetate (200 mL) and water (200 mL). The aqueous layer was extracted with ethyl acetate (100 mL×2). The combined organic layers were washed with saturated aqueous sodium chloride (30 mL×2), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo and the residue was purified by silica gel chromatography eluted with PE to give the title compound 17c as a white solid (26.0 g, 87.2%, HPLC: 97.45%). The compound was characterized by the following spectroscopic data: 1H NMR (400 MHz, CDCl3) δ(ppm): 7.54 (d, 1H), 7.45 (m, 1H), 7.40 (d, 1H), 7.18 (d, 2H), 7.00 (d, 2H), 4.80-4.64 (m, 2H), 4.01 (s, 2H).

Workup

  1. temperatureThe reaction mixture was warmed up to 140° C.
  2. stirringstirred for 12 hours
  3. temperatureThe mixture was cooled to room temperature
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo
  6. customthe residue was partitioned between ethylacetate (200 mL) and water (200 mL)
  7. extractionThe aqueous layer was extracted with ethyl acetate (100 mL×2)
  8. washThe combined organic layers were washed with saturated aqueous sodium chloride (30 mL×2)
  9. dry with materialdried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. concentrationThe filtrate was concentrated in vacuo
  12. customthe residue was purified by silica gel chromatography
  13. washeluted with PE

Sources & evidence

ORD record
ord-22378d1a73c64a37a0fd2bf927786a65
Source dataset
uspto-grants-2016_07
Patent number
US09394329B2

Reaction notes

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