(4-Chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanone → (4-Chlorophenyl)(1-methyl-1H-imidazol-5-yl)(3-phenyl-2,4-bis(trifluoromethyl)quinolin-6-yl)methanol

HRID 627559Notes

Reaction equation

HRID 627559 reaction equation
C([Mg]Cl)(C)C.Br[C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[N:13]=[C:12]([C:17]([F:20])([F:19])[F:18])[C:11]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[C:10]2[C:27]([F:30])([F:29])[F:28].[Cl:31][C:32]1[CH:37]=[CH:36][C:35]([C:38]([C:40]2[N:44]([CH3:45])[CH:43]=[N:42][CH:41]=2)=[O:39])=[CH:34][CH:33]=1>C1COCC1>[Cl:31][C:32]1[CH:33]=[CH:34][C:35]([C:38]([C:40]2[N:44]([CH3:45])[CH:43]=[N:42][CH:41]=2)([C:7]2[CH:8]=[C:9]3[C:14](=[CH:15][CH:16]=2)[N:13]=[C:12]([C:17]([F:20])([F:19])[F:18])[C:11]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[C:10]3[C:27]([F:28])([F:30])[F:29])[OH:39])=[CH:36][CH:37]=1

Participants

5

Reactant 3

HCID 11521405(4-Chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanone2×HCID 867160666-Bromo-3-phenyl-2,4-bis(trifluoromethyl)quinoline2×HCID 178418918HCID 178418918, compound

Product 1

HCID 86716130(4-Chlorophenyl)(1-methyl-1H-imidazol-5-yl)(3-phenyl-2,4-bis(trifluoromethyl)quinolin-6-yl)methanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

Isopropylmagnesium chloride (2.0 M in THF, 0.532 mL, 1.06 mmol) was added dropwise to a solution of 6-iodo-3-phenyl-2,4-bis(trifluoromethyl)quinoline (474 mg, 1.01 mmol, Intermediate 8, step d) in THF (1 mL) at −78° C. under an argon atmosphere. The mixture was stirred at −78° C. for 5 min, then was removed from the cold bath and was stirred for 15 min. Neat (4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanone (246 mg, 1.12 mmol, Intermediate 18, step b) was added followed by 1 mL THF to aid stirring of the thick mixture. The mixture was stirred at room temperature overnight. The reaction was quenched by addition of saturated aqueous NH4Cl and extracted with EtOAc (three times). The organic phase was dried (Na2SO4), filtered, and concentrated. The residue was purified by flash column chromatography (silica gel, gradient 0-3% MeOH-DCM) to afford the title compound. 1H NMR (400 MHz, CDCl3) δ 8.36 (d, J=1.71 Hz, 1H), 8.29 (d, J=8.80 Hz, 1H), 7.89 (dd, J=1.59, 8.93 Hz, 1H), 7.41-7.52 (m, 3H), 7.38 (s, 1H), 7.32-7.37 (m, 4H), 7.28-7.31 (m, 2H), 6.43 (s, 1H), 3.40 (s, 3H); MS m/e 562.0 [M+H]+.

Workup

  1. customwas removed from the cold bath
  2. stirringwas stirred for 15 min
  3. stirringto aid stirring of the thick mixture
  4. stirringThe mixture was stirred at room temperature overnight
  5. customThe reaction was quenched by addition of saturated aqueous NH4Cl
  6. extractionextracted with EtOAc (three times)
  7. dry with materialThe organic phase was dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by flash column chromatography (silica gel, gradient 0-3% MeOH-DCM)

Sources & evidence

ORD record
ord-293f6faff31845749cdc69664935e2b8
Source dataset
uspto-grants-2016_04
Patent number
US09309222B2

Reaction notes

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