p-Toluenesulfonic acid → HCID 12001404, compound

Participants

Reaction Steps

To a solution of compound 20a in anhydrous THF (15 ml) was added triethyl orthoformate (0.75 ml, 4.4 mmol) and a catalytic amount of p-toluenesulphonic acid. The resultant mixture was stirred at reflux for 1 hour. The solvent was removed in vacuo and the residue was purified by column chromatography on silica gel, eluting with a mixture of ethyl acetate and methanol (9:1 v/v). Compound 21a (0.87 g) was precipitated as the hydro chloride by addition of etheral hydrogen chloride to the pure fractions. LC-ESI-HRMS of [M+H]+ shows 388.14 Da. Calc. 388.138519 Da, dev. 3.8 ppm The following compounds were prepared in analogy herewith: 1-[3-(2-Ethyl-2H-[1,2,4]triazol-3-ylmethoxymethyl)-phenyl]-5-trifluoromethyl-1H-benzoimidazole (21b) from compound 20b. Yield: 67%. LC-ESI-HRMS of [M+H]+ shows 402.1548 Da. Calc. 402.154169 Da, dev. 1.6 ppm 5-Methyl-1-[3-(2-methyl-2H-[1,2,4]triazol-3-ylmethoxymethyl)-phenyl]-1H-benzoimidazole (21c) from compound 20c. Yield: 7% (3 steps). LC-ESI-HRMS of [M+H]+ shows 334.1679 Da. Calc. 334.166785 Da, dev. 3.3 ppm 1-{1-[3-(2-Methyl-2H-[1,2,4]triazol-3-ylmethoxymethyl)-phenyl]-1H-benzoimidazol-5-yl}-ethanone (21d) from compound 20d. Yield: 53% isolated as the free base. Mp 121.4-123.6° C.

Provenance & Evidence