Hydrochloric Acid → (4-Fluorophenyl)(1-methyl-1H-imidazol-5-yl)methanone

A clear colorless solution of 5-bromo-N-methyl-imidazole (47.7 g, 296 mmol) in THF (500 mL) was placed in an ice bath and ethylmagnesium bromide in diethyl ether (3.0 M, 98.7 mL, 296 mmol) was added via syringe fairly rapidly, over 17 min. The thick suspension was stirred at room temperature for 20 min. The mixture was again cooled in an ice water bath before addition of neat 4-fluoro-N-methoxy-N-methylbenzamide (45.2 g, 247 mmol, Intermediate 49, step a). The resulting suspension was stirred overnight at room temperature. To the reaction mixture was added saturated aqueous NH4Cl (100 mL) followed by water (200 mL). The pH was adjusted to 7 by addition of 1 N aqueous HCl, the mixture was partially concentrated to remove THF, and was extracted with EtOAc (3×). The organic phase was dried (Na2SO4), filtered, and concentrated. The crude product was triturated with EtOAc:heptane(1:1, 150 mL) to afford the title compound as a white crystalline solid.

1. stirringThe resulting suspension was stirred overnight at room temperature
2. concentrationthe mixture was partially concentrated
3. customto remove THF
4. extractionwas extracted with EtOAc (3×)
5. dry with materialThe organic phase was dried (Na2SO4)
6. filtrationfiltered
7. concentrationconcentrated
8. customThe crude product was triturated with EtOAc:heptane(1:1, 150 mL)

ORD record

ord-e91aaccb70594683b766811ae556da8c

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09309222B2