2-(1-methyl-1H-pyrazol-4-yl)-3-oxopropanenitrile synthesis

Yield:1039364-93-6 95%

Reaction Conditions:

with potassium tert-butylate in 1,2-dimethoxyethane at 85; for 29 h;

Steps:

5

The compound of formula Xl (10.49 g, 86.68 mmol) and ethyl formate (15.15 ml_, 187.5 mmol, 2.16 equiv.) were dissolved in anhydrous DME (25 ml_) and added drop-wise to a suspension of potassium- terf-butoxide (17.01 g of 95%, 144.3 mmol, 1.66 equiv.) in anhydrous DME (90 ml_) in an open pressure tube. After addition was complete, the tube was sealed and stirred at 85 ⁰C for 29 hours. After cooling, the resulting thick suspension was diluted with water (400 ml_) to yield a solution of pH 8, and was extracted with ethyl acetate (3 x 400 ml_). The aqueous solution was then acidified to pH 4 with concentrated hydrochloric acid (11 ml_) resulting in the formation of a white precipitate. This suspension was then filtered, and the recovered solid was washed with water and dried under vacuum to yield the compound of formula XII as an off-white solid (11.66 g, 90% yield). Extraction of the aqueous filtrate with ethyl acetate (2 x 500 ml_), followed by washing with brine, drying with sodium sulfate, filtering and concentrating resulted in an additional quantity of the product (0.74 g, 5% yield).

References:

WO2008/153870,2008,A1 Location in patent:Page/Page column 31