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

HRID 1913047Notes

Reaction equation

HRID 1913047 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-].[Cs+].[Cs+].CC1C=CC(S(O[CH2:34][C:35]([F:38])([F:37])[F:36])(=O)=O)=CC=1>CN(C=O)C>[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][CH2:34][C:35]([F:38])([F:37])[F:36])=[CH:11][CH:10]=2)[CH:7]=1

Participants

5

Reactant 3

HCID 10796Cesium 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]benzene

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-[(5-bromo-2-chloro-phenyl)methyl]phenol 7c (14.5 g, 48.7 mmol, prepared according to the method in WO2009026537) was dissolved in 300 mL DMF, followed by addition of cesium carbonate (31.7 g, 97.5 mmol). The reaction mixture was stirred for 10 minutes. The reaction mixture was stirred for 8 hours at 80° C. after 2,2,2-trifluoroethyl-4-methylbenzenesulfonate 7b (12.4 g, 48.7 mmol) was added. Thereafter, the reaction mixture was filtered and washed with a small amount of ethyl acetate before the filtrate was concentrated under reduced pressure. The resulting residue was partitioned after 100 mL water and 50 mL saturated sodium chloride solution were added. The aqueous phase was extracted with ethyl acetate (100 mL×3) and the organic extract was washed with saturated sodium chloride solution (100 mL), combined and concentrated. The resulting residue was purified by silica gel chromatography with elution system B to obtain the title compound 4-bromo-1-chloro-2-[[4-(2,2,2-trifluoroethoxy)phenyl]methyl]benzene 7d (7.26 g, white solid), yield: 39.2%. 1H NMR (400 MHz, CDCl3): δ 7.32 (s, 1H), 7.30-7.24 (m, 2H), 7.21-7.14 (m, 2H), 6.98-6.87 (m, 2H), 4.38 (d, 2H), 4.06 (s, 2H).

Workup

  1. additionwas added
  2. filtrationThereafter, the reaction mixture was filtered
  3. washwashed with a small amount of ethyl acetate before the filtrate
  4. concentrationwas concentrated under reduced pressure
  5. customThe resulting residue was partitioned after 100 mL water and 50 mL saturated sodium chloride solution
  6. additionwere added
  7. extractionThe aqueous phase was extracted with ethyl acetate (100 mL×3)
  8. extractionthe organic extract
  9. washwas washed with saturated sodium chloride solution (100 mL)
  10. concentrationconcentrated
  11. customThe resulting residue was purified by silica gel chromatography with elution system B

Sources & evidence

ORD record
ord-8e42ba1e6d974108a2f483417acd67be
Source dataset
uspto-grants-2013_12
Patent number
US08609622B2

Reaction notes

Loading…