(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

Temperature

-78 °C

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]+.

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)

ORD record

ord-293f6faff31845749cdc69664935e2b8

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09309222B2