1-Bromo-4-(trifluoromethoxy)benzene → HCID 59837911, compound

HRID 272655Notes

Reaction equation

HRID 272655 reaction equation
[Mg].Br[C:3]1[CH:8]=[CH:7][C:6]([O:9][C:10]([F:13])([F:12])[F:11])=[CH:5][CH:4]=1.[Br:14][C:15]1[CH:16]=[C:17]([CH:25]=[CH:26][CH:27]=1)[C:18]([C:20]1[NH:21][CH:22]=[CH:23][N:24]=1)=[O:19]>C1COCC1.C(OCC)(=O)C.O.[Cl-].[NH4+].[Cu]I>[Br:14][C:15]1[CH:16]=[C:17]([C:18]([C:20]2[NH:24][CH:23]=[CH:22][N:21]=2)([C:3]2[CH:8]=[CH:7][C:6]([O:9][C:10]([F:13])([F:12])[F:11])=[CH:5][CH:4]=2)[OH:19])[CH:25]=[CH:26][CH:27]=1

Participants

9

Reactant 3

HCID 5210081-Bromo-4-(trifluoromethoxy)benzeneHCID 3418429(3-Bromophenyl)-1H-imidazol-2-ylmethanoneHCID 5462224Magnesium

Product 1

HCID 59837911HCID 59837911, compoundYield 81%

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of magnesium (0.644 g, 87.7 mmol) in THF (13 mL) at 50° C. is treated dropwise with a solution of 1-bromo-4-(trifluoromethoxy)benzene (6.32 g, 26.2 mmol) in THF over a period of 5 min, stirred at 50° C. for an additional 1.5 h, cooled to room temperature, treated with copper(I) iodide (0.041 g, 0.215 mmol) and a solution of 2-(3-bromobenzoyl)-1H-imidazole (2.60 g, 10.4 mmol) in THF, heated at 65° C. overnight, cooled to room temperature and diluted with a 1:1:1 mixture of ethyl acetate, water and saturated aqueous ammonium chloride. The phases are separated and the aqueous phase is extracted with ethyl acetate. The combined organic extracts are dried over sodium sulfate, filtered and concentrated. The resultant residue is purified by flash chromatography (silica, 85:15 to 75:25 hexanes/ethyl acetate as eluent) affords the title product as a yellow solid, 3.47 g (81% yield), identified by NMR and mass spectral analyses. 1H NMR (500 MHz, CDCl3) δ 8.98 (br s, 1H), 7.55 (t, J=1.6 Hz, 1H), 7.45 (dt, J=8.1, 1.9 Hz, 1H), 7.37-7.34 (m, 2H), 7.24-7.20 (m, 2H), 7.18 (d, J=8.1 Hz, 2H), 7.07 (br s, 1H), 6.98 (br s, 1H), 4.30 (br s, 1H); ESI MS m/z 412 [C17H12BrF3N2O2+H]+.

Workup

  1. temperaturecooled to room temperature
  2. temperaturecooled to room temperature
  3. customThe phases are separated
  4. extractionthe aqueous phase is extracted with ethyl acetate
  5. dry with materialThe combined organic extracts are dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resultant residue is purified by flash chromatography (silica, 85:15 to 75:25 hexanes/ethyl acetate as eluent)

Sources & evidence

ORD record
ord-7fd60464afdc46a8b5acd44ed4909af3
Source dataset
uspto-grants-2008_11
Patent number
US07456186B2

Reaction notes

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