Pivaloyl chloride → N-{2-tert-Butyl-1-[(4,4-difluorocyclohexyl)methyl]-1H-benzimidazol-5-yl}acetamide

Participants

Reaction Steps

N-(3-Amino-4-{[(4,4-difluorocyclohexyl)methyl]amino}phenyl)acetamide (1.32 g, 4.44 mmol) was dissolved in 100 mL of DCM containing DMAP (108 mg, 0.89 mmol). Trimethylacetyl chloride (0.60 mL, 4.88 mmol) was added dropwise and the solution was stirred at rt for 2 h. The solution washed with saturated aqueous NaHCO3 solution, saturated aqueous NaCl solution and dried over anhydrous Na2SO4. Part of the product precipitated during the washings and was filtered. The organic phase was evaporated and combined with the precipitate. The product was dissolved in 30 mL of AcOH and placed in 6 sealed tubes (5 mL/tube). Each tube was heated at 150° C. in a Personal Chemistry microwaves instrument for 2.5 h. The fractions were pooled and the solvent was evaporated. The product was dissolved in EtOAc and washed with aqueous NaHCO3 solution, saturated aqueous NaCl solution and dried over anhydrous Na2SO4. The product was purified by flash chromatography on silica gel using acetone/hexanes (2:1) as eluent. Yield: 1.11 g (68%); 1H NMR (400 MHz, CD3OD) δ 1.40-1.49 (m, 2 H), 1.52 (s, 9 H), 1.60-1.65 (m, 2 H), 1.67-1.77 (m, 1 H), 1.96-2.06 (m, 3 H), 2.11 (s, 3 H), 2.15-2.23 (m, 1 H), 4.28 (d, J=7.62 Hz, 2 H), 7.35-7.39 (m, 1 H), 7.40-7.44 (m, 1 H), 7.85 (d, J=1.76 Hz, 1 H).

Provenance & Evidence