Trimethyl orthoformate → N-[5-(1,1-dimethoxy-ethyl)-pyrazin-2-yl]-2,2-dimethyl-propionamide

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Reaction Steps

A suspension of N-(5-acetyl-pyrazin-2-yl)-2,2-dimethyl-propionamide (prepared as in Example 28, 2.00 g, 9.038 mmol) in trimethyl orthoformate (13.5 mL) and methanol (36 mL) was treated with p-toluenesulfonic acid monohydrate (174.5 mg, 0.904 mmol). The resulting reaction mixture was heated under reflux for 2.5 h and then concentrated in vacuo. The residue was diluted with ethyl acetate (200 mL). The organic layer was washed with a saturated aqueous sodium bicarbonate solution (100 mL) and a saturated aqueous sodium chloride solution (100 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40L, Silica, 1/4 ethyl acetate/hexanes) afforded N-[5-(1,1-dimethoxy-ethyl)-pyrazin-2-yl]-2,2-dimethyl-propionamide as a white solid (1.74 g, 72%): mp 108–109° C.; EI-HRMS m/e calcd for C13H21N3O3 (M+) 267.1583, found 267.1486.

Provenance & Evidence