Sodium Bicarbonate → 5-(Benzoxazol-2-yl)-2-hydroxymethyl-1-(tetrahydropyran-4-yl)benzimidazole

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Reaction Steps

An eggplant flask (50 mL) was charged with 2-acetoxymethyl-5-(2-hydroxyanilinocarbonyl)-1-(tetrahydropyran-4-yl)benzimidazole (see Working Example 13-1) (0.50 g, 1.22 mmol) toluene (6.3 mL), and p-toluenesulfonic acid hydrate (1.60 g, 8.41 mmol), and this was refluxed for 1.5 hours. After being allowed to cool, the liquid was made neutral with saturated aqueous sodium hydrogen carbonate. The precipitated crystals were filtered off and washed successively with toluene and hexane, then dried under reduced pressure with heating to yield a mixture of the title compound and 5-(benzoxazol-5-yl)-2-acetoxymethyl-1-(tetrahydropyran-4-yl)benzimidazole (0.25 g: estimated to contain 0.57 mmol and 0.13 mmol, respectively, according to 1H-NMR) as a white powder. This mixture and methanol (7 mL) were charged to an eggplant flask (50 mL) to which was then added an aqueous solution of lithium hydroxide (1 M, 0.3 mL), and after stirring for 30 m the liquid was made pH 6 with dilute hydrochloric acid (1 M). The precipitated crystals were filtered off, washed with distilled water, and dried under reduced pressure with heating to yield the title compound (0.07 g, 16.4% yield) as a light pinkish-white powder.

Provenance & Evidence