(4-Chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanone → (3-Benzyl-2,4-dichloroquinolin-6-yl)(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanol

HRID 928830Notes

Reaction equation

HRID 928830 reaction equation
[Cl:1][C:2]1[C:11]([CH2:12][C:13]2[CH:18]=[CH:17][C:16](C(F)(F)F)=[CH:15][CH:14]=2)=[C:10]([Cl:23])[C:9]2[C:4](=[CH:5][CH:6]=[C:7](I)[CH:8]=2)[N:3]=1.[Li]CCCC.[Cl:30][C:31]1[CH:36]=[CH:35][C:34]([C:37]([C:39]2[N:43]([CH3:44])[CH:42]=[N:41][CH:40]=2)=[O:38])=[CH:33][CH:32]=1>O1CCCC1>[CH2:12]([C:11]1[C:2]([Cl:1])=[N:3][C:4]2[C:9]([C:10]=1[Cl:23])=[CH:8][C:7]([C:37]([C:34]1[CH:33]=[CH:32][C:31]([Cl:30])=[CH:36][CH:35]=1)([C:39]1[N:43]([CH3:44])[CH:42]=[N:41][CH:40]=1)[OH:38])=[CH:6][CH:5]=2)[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

5

Reactant 3

HCID 11521405(4-Chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanone2×HCID 867156552,4-Dichloro-6-iodo-3-(4-(trifluoromethyl)benzyl)quinoline2×HCID 178418339Butyllithium

Product 1

HCID 74221196(3-Benzyl-2,4-dichloroquinolin-6-yl)(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Into a 25-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 3-benzyl-6-bromo-2,4-dichloroquinoline (500 mg, 1.36 mmol, Intermediate 2: step c) in tetrahydrofuran (10 mL). n-BuLi (0.6 mL, 2.5 M in hexanes) was then added at −78° C. The resulting solution was stirred for 1 hour at −78° C. (4-Chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanone (301 mg, 1.36 mmol, Intermediate 1: step b) was added to this solution. The resulting solution was allowed to react, with stirring, for an additional 8 hours at room temperature. The reaction was then quenched by the addition of 10 mL of water/ice. The resulting solution was extracted with 3×20 mL of ethyl acetate. The combined organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was purified by chromatography over a silica gel column with dichloromethane/methanol to give the title compound as a white solid. 1H NMR (400 MHz, DMSO-d6) δ=8.20 (s, 1H), 8.01 (d, J=8.5 Hz, 1H), 7.69-7.79 (m, 2H), 7.44 (d, J=7.5 Hz, 2H), 7.25-7.37 (m, 4H), 7.14-7.25 (m, 4H), 6.20 (s, 1H), 4.47 (s, 2H), 3.31 (s, 3H); MS m/e 508 [M+H]+.

Workup

  1. customInto a 25-mL round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. additionwas added to this solution
  4. customto react
  5. customThe reaction was then quenched by the addition of 10 mL of water/ice
  6. extractionThe resulting solution was extracted with 3×20 mL of ethyl acetate
  7. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under vacuum
  10. customThe residue was purified by chromatography over a silica gel column with dichloromethane/methanol

Sources & evidence

ORD record
ord-5f0f5be8694d4d6f8c4e08cb73e4595c
Source dataset
uspto-grants-2016_03
Patent number
US09290476B2

Reaction notes

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