5-(cyclopropylmethoxy)-2-Pyrazinecarboxylic acid synthesis

Yield:1286777-19-2 34%

Reaction Conditions:

Stage #1: Cyclopropylmethanol;5-chloropyrazinoic acidwith potassium hydroxide in dimethyl sulfoxide at 80; for 1.5 h;Microwave irradiation;
Stage #2: with citric acid in water;

Steps:

I.16

The 5-cyclopropylmethoxy-pyrazine-2-carboxylic acid was obtained following the general procedure below:A solution of 5-chloro-pyrazine-2-carboxylic acid (1.50 g, 9.46 mmol) in dry dimethylsulfoxide (5 ml) was treated at 25° C. with cyclopropyl-methanol (1.02 g, 14.1 mmol) and powdered potassium hydroxide (2.12 g, 37.4 mmol). The mixture was heated in a microwave oven at 80° C. for 90 minutes. For the workup, the reaction mixture was quenched with an aqueous solution of citric acid (10%), then extracted with ethyl acetate (5×30 ml), followed by the extraction with a 4:1-mixture of dichloromethane and methanol. The combined organic layers were washed with brine (200 ml), dried and evaporated ate reduced pressure. After lyophilization the 5-cyclopropylmethoxy-pyrazine-2-carboxylic acid (34% yield) was obtained as a white solid. MS (ISP): m/z=195.0 [M+H]⁺.

References:

US2012/258962,2012,A1 Location in patent:Page/Page column 42