Citric Acid → tert-butyl 2-cyano-2-(1-methyl-1H-pyrazol-5-yl)acetate

Participants

Reaction Conditions

Reaction Steps

To a solution of tert-butyl cyanoacetate (340 μL, 2.40 mmol) in 1,4-dioxane (5 mL) was added potassium t-butoxide (1M in tetrahydrofuran, 5 mL, 5.0 mmol) at room temperature. After 10 min, a solution of 5-iodo-1-methyl-1H-pyrazole (500 mg, 2.40 mmol) in 1,4-dioxane (5 mL) and tetrakis(triphenylphosphine)palladium(0) (75 mg, 0.065 mmol) were added. The reaction mixture was stirred for 16 h at 70° C. The mixture was cooled and then was diluted with diethyl ether (50 mL) and a 10% aqueous solution of citric acid. The organic layer was separated and the aqueous layer was extracted with diethyl ether (2×10 mL). The combined organics were washed with brine (15 mL), dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (Gradient: 30% to 40% ethyl acetate in heptane) to afford tert-butyl 2-cyano-2-(1-methyl-1H-pyrazol-5-yl)acetate (132.8 mg) as a pale brown oil. MS (ES+) (M+H) 222.0, LCMS retention time: 2.74 min (Method L); 1H NMR (500 MHz, CDCl3) δ 1.50 (s, 9H), 3.93 (s, 3H), 4.80 (s, 1H), 6.39 (d, 1H), 7.48 (d 1H).

Provenance & Evidence