Potassium Carbonate → N-methoxy-N-methyl-3-{[5-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,3-benzodiazol-2-yl]methyl}cyclobutane-1-carboxamide

Participants

Reaction Steps

K2CO3 (381 mg, 2.76 mmol), followed by SEM-Cl (430 μl, 2.43 mmol) was added to a solution of the N-methoxy-N-methyl-3-{[5-(trifluoromethyl)-1H-1,3-benzodiazol-2-yl]methyl}cyclobutane-1-carboxamide (754 mg, 2.21 mmol) in DMF (10 ml) at RT and stirred overnight. The reaction was monitored by LCMS. The reaction mixture was diluted with water (3 ml), brine (30 ml) and then extracted with EtOAc (2×50 ml). This was dried over Na2SO4, filtered and evaporated to give a clear orange oil. Purification by silica gel column chromatography, eluting with EtOAc:heptanes (1:1-1) gave the desired products as a beige oils as a single regioisomer (217 mg, 21%); MS (ESI+) for C22H32F3N3O3Si m/z 472.55 [M+H]+; HPLC purity 99% (ret. time, 2.37 min); 1H NMR (250 MHz, CHLOROFORM-d) δH ppm −0.31-0.22 (9 H, m), 0.83-1.00 (2 H, m), 2.03-2.25 (2 H, m), 2.30-2.74 (2 H, m), 2.85-3.14 (3 H, m), 3.18 (3 H, s), 3.32-3.60 (3 H, m), 3.61-3.72 (3 H, m), 5.52 (2 H, s), 7.51 (1 H, dd, J=8.38, 1.22 Hz), 7.70 (1 H, s), 7.79 (1 H, d, J=8.53 Hz) and as a mixture of regioisomers (280 mg, 27%); C22H32F3N3O3Si m/z 472.55 [M+H]+; HPLC purity 72% & 21% (ret. time, 2.39 & 2.36 min); 1H NMR (250 MHz, CHLOROFORM-d) δ ppm −0.08-0.01 (9 H, m), 0.81-0.99 (2 H, m), 1.94-2.24 (2 H, m), 2.38-2.74 (2 H, m), 2.90-3.14 (3 H, m), 3.14-3.22 (3 H, m), 3.33-3.63 (3 H, m), 3.63-3.70 (3 H, m), 5.40-5.64 (2 H, m), 7.40-7.74 (2 H, m), 7.75-8.14 (1 H, m).

Provenance & Evidence