HCID 71711558, compound → (2,4-Dichloro-3-(3-fluorophenyl)-8-methylquinolin-6-yl)(4-fluorophenyl)(1-methyl-1H-imidazol-5-yl)methanol

HRID 627574Notes

Reaction equation

HRID 627574 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([CH3:12])[CH:11]=1)[N:8]=[C:7]([Cl:13])[C:6]([C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=1)=[C:5]2[Cl:21].[F:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]([C:31]2[N:35]([CH3:36])[CH:34]=[N:33][CH:32]=2)=[O:30])=[CH:25][CH:24]=1.[Li]CCCC>>[Cl:13][C:7]1[C:6]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=2)=[C:5]([Cl:21])[C:4]2[C:9](=[C:10]([CH3:12])[CH:11]=[C:2]([C:29]([C:26]3[CH:27]=[CH:28][C:23]([F:22])=[CH:24][CH:25]=3)([C:31]3[N:35]([CH3:36])[CH:34]=[N:33][CH:32]=3)[OH:30])[CH:3]=2)[N:8]=1

Participants

4

Reactant 3

HCID 71711558HCID 71711558, compound2×HCID 867160976-Bromo-2,4-dichloro-3-(3-fluorophenyl)-8-methylquinoline2×HCID 178418339Butyllithium

Product 1

HCID 86716155(2,4-Dichloro-3-(3-fluorophenyl)-8-methylquinolin-6-yl)(4-fluorophenyl)(1-methyl-1H-imidazol-5-yl)methanol

Conditions

Temperature
-78 °C

Procedure

A round bottom flask was charged with 6-bromo-2,4-dichloro-3-(3-fluorophenyl)-8-methylquinoline (1.00 g, 2.60 mmol, Intermediate 50, step c) and (4-fluorophenyl)(1-methyl-1H-imidazol-5-yl)methanone (583 mg, 2.86 mmol, Intermediate 49, step b) and was evacuated and re-filled with argon (three times). THF (20 mL) was added, and the solution was cooled in a dry ice acetone bath for 2 minutes. At this point the mixture began to turn cloudy and n-BuLi (1.6 M in hexane, 2.11 mL, 3.38 mmol), was added over about 1 minute. The mixture was stirred at −78° C. for 10 minutes, then in an ice water bath for 1 hour. The reaction was quenched by addition of saturated aqueous NH4Cl, diluted with water and extracted with EtOAc (3×). The organic phase was dried (Na2SO4), filtered, and concentrated. The residue was purified by flash column chromatography (silica gel, 30-60% acetone-DCM) to afford slightly impure title compound as an off-white solid. 1H NMR (400 MHz, CHLOROFORM-d) δ 8.09 (s, 1H), 7.60 (s, 1H), 7.44-7.55 (m, 1H), 7.30-7.39 (m, 3H), 7.15-7.23 (m, 1H), 7.01-7.12 (m, 4H), 6.40 (s, 1H), 4.00 (br. s., 1H), 3.40 (s, 3H), 2.74 (s, 3H). MS m/e 510.1 [M+H]+.

Workup

  1. customwas evacuated
  2. additionre-filled with argon (three times)
  3. additionTHF (20 mL) was added
  4. temperaturethe solution was cooled in a dry ice acetone bath for 2 minutes
  5. additionwas added over about 1 minute
  6. waitin an ice water bath for 1 hour
  7. customThe reaction was quenched by addition of saturated aqueous NH4Cl
  8. additiondiluted with water
  9. extractionextracted with EtOAc (3×)
  10. dry with materialThe organic phase was dried (Na2SO4)
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe residue was purified by flash column chromatography (silica gel, 30-60% acetone-DCM)

Sources & evidence

ORD record
ord-b9c96b407c334ea2886876e16b647319
Source dataset
uspto-grants-2016_04
Patent number
US09309222B2

Reaction notes

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