Methyl iodide → tert-butyl (4-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazol-5-yl)methyl(methyl)carbamate

Participants

Reaction Steps

To a solution of 216 (620 mg, 1.7 mmol) in DMF (8 mL) at 0° C. was added NaH (102 mg, 2.54 mmol, 60% in oil). The reaction was warmed to RT and stirred for 25 min then re-cooled to 0° C. and iodomethane (0.19 mL, 3.05 mmol) was added. The reaction was warmed to RT and stirred for 3 h. The conversion was low so the reaction mixture was cooled back to 0° C. and additional NaH (67 mg, 1.69 mmol, 60% in oil) was added. The reaction was warmed to RT and stirred for 20 min, re-cooled to 0° C. and iodomethane (0.11 mL, 1.69 mmol) was added. The reaction was warmed to RT and stirred for 3 h then partitioned between EtOAc and H2O. The combined organic extracts were thrice washed with H2O, dried (Na2SO4), filtered and concentrated in vacuo. The crude residue was purified by SiO2 chromatography to afford 363 mg (56%) of tert-butyl (4-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazol-5-yl)methyl(methyl)carbamate (218): MS (ESI) m/z=380.2 [M+1]+.

Provenance & Evidence