Hydrochloric Acid → 4-bromo-2-(fluoromethyl)-1-(2-methyl-3-(trifluoromethyl)benzyl)-1H-benzo[d]imidazol-6-amine

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-bromo-2-(fluoromethyl)-1-(2-methyl-3-(trifluoromethyl)benzyl)-6-nitro-1H-benzo[d]imidazole (3.05 g, 6.84 mmol) in Methanol (40 mL) in a 250 ml round bottomed flask was added Tin(II)chloride dihydrate (9.25 g, 41.0 mmol) and HCl (1.869 mL, 61.5 mmol). The reaction mixture was left to stir at 50° C. for 1 h; reaction mostly complete with a very small amt of starting material and a very small amt of des-fluoro product. The solvent was removed and diluted with water (100 mL) and this solution was decanted into a 250 mL Erlenmeyer flask. This solution was neutralized with 6N NaOH to pH 9—a white solid was observed. The brown residue in the rb flask was dissolved in 100 mL of EtOAc and washed with 1N NaOH, brine, dried and evaporated to yield a brown oil. The water layer was extracted with EtOAc to which yielded an additional oil. The oils were combined and purified by reversed phase HPLC; eluted with a gradient of acetonitrile (0.1% TFA) and water (0.1% TFA v/v) (25-70%) over 12 minutes. The fractions were collected and evaporated to yield the expected compound 4-bromo-2-(fluoromethyl)-1-(2-methyl-3-(trifluoromethyl)benzyl)-1H-benzo[d]imidazol-6-amine (2.3 g, 5.53 mmol, 81% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.54 (s, 3H) 5.39 (s, 2H) 5.51 (s, 1H) 5.63 (s, 1H) 6.32 (d, J=2.02 Hz, 1H) 6.56 (d, J=7.83 Hz, 1H) 6.96 (d, J=2.02 Hz, 1H) 7.16 (t, J=7.83 Hz, 1H) 7.61 (d, J=7.83 Hz, 1H); LC/MS: MS (ES+) m/e 417 [M+H]+.

Provenance & Evidence