Acetonitrile, 2,2-diethoxy- → Methyl 2,2-diethoxyethanecarboximidate

Participants

Reaction Steps

A 1-L, 3-necked round bottom flask was charged with a solution prepared from sodium methoxide (9.41 g, 0.174 mol, 0.9 equiv) in anhydrous methanol (150 mL). A solution of diethoxyacetonitrile (25 g, 0.193 mol) in anhydrous methanol (70 mL), was added to the methoxide solution, slowly, over 15 min, via an addition funnel. The reaction was then stirred overnight at room temperature, and the excess methanol was evaporated, in vacuo. The resulting oil was diluted with water and extracted into ethyl acetate (2×250 mL), then CH2Cl2 (2×250 mL). The organic phases were combined and dried over Na2SO4, filtered and concentrated in vacuo affording 9 g, (29%) of crude methyl 2,2-diethoxyethanimidoate having a purity of 80–85% by 1H NMR. This was used in the next step without further purification. A 500-mL round bottom flask was charged with a solution of the amidrazone from Step 1, N′-methylpyridine-2-carbohydrazonamide (22 g, 0.0548 mol) in methanol (75 mL), along with a solution of the crude imidate ester (8.84 g, 0.0548 mol) in methanol (75 mL). The mixture was treated with glacial acetic acid (4.75 mL, 1.5 equiv), and stirred at room temperature overnight while monitoring by LC/MS for disappearance of the amidrazone. The methanol was evaporated in vacuo, and the resulting oil was neutralized with saturated, aqueous NaHCO3. The product was extracted into ethyl acetate (3×150 mL) and the organic phase dried over Na2SO4, filtered and concentrated, to give a yellow oil (11.06 g, 76% crude yield) of the acetal intermediate that was used in the next step without purification.

Provenance & Evidence