Pivaloyl chloride → Methyl [2-tert-butyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazol-5-yl]carbamate

Participants

Reaction Steps

Methyl {3-amino-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}carbamate (2.29 g, 8.20 mmol) and DMAP (0.20 g, 1.64 mmol) were dissolved in 75 mL of DCM. Trimethylacetyl chloride (1.10 mL, 9.02 mmol) was added dropwise and the solution was stirred at rt for 2 h. The solution was washed with aqueous NaHCO3 solution, brine and dried over anhydrous MgSO4. The residue was dissolved in 25 mL of AcOH and was heated at 125° C. for 1 h using a Personal Chemistry microwave apparatus. The solvent was evaporated. The residue was dissolved in EtOAc and washed with aqueous NaHCO3 solution, brine and dried over anhydrous MgSO4. The crude product was purified by silica gel flash chromatography using 4:3/hexanes: acetone as eluent. Yield: 1.81 g (64%). 1H NMR (400 MHz, CHLOROFORM-D) δ 1.48-1.54 (m, 4 H), 1.56 (s, 9 H), 2.23-2.35 (m, 1 H), 3.27-3.35 (m, 2 H), 3.78 (s, 3 H), 3.96 (t, J=2.93 Hz, 1 H), 3.99 (t, J=3.03 Hz, 1 H), 4.18 (d, J=7.42 Hz, 2 H), 6.63 (br.s, 1 H), 7.24-7.28 (m, 1 H), 7.41 (br.s, 1 H), 7.61 (d, J=1.95 Hz, 1 H).

Provenance & Evidence