N-Acetyl-L-Cysteine → 2-(Pyrimidin-2-yl)pyrimidine-5-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

A pressure vessel is charged with 2-cyanopyrimidine (7.88 g, 75 mmol), N-acetyl cysteine (1.22 g, 7.5 mmol), ammonium acetate (6.93 g, 90 mmol), and MeOH (75 mL). The vessel is sealed and heated at 110° C. for 1.5 h, and then cooled to rt. To the reaction mixture is added sodium 2-ethoxycarbonyl-3-oxo-but-1-en-1-olate (17 g, 86.25 mmol) and MeOH (75 mL). The mixture is heated to reflux for 1.5 h and then cooled to rt. NaOH (6 g, 150 mmol) and water (80 mL) are added. The mixture is stirred for 30 min or until LC-MS indicates complete hydrolysis of the intermediate ester. The pH of the reaction mixture is adjusted to 3 with concentrated (12 M) aqueous HCl. MeOH is evaporated in vacuo, and the resulting precipitate is collected via filtration and washed with minimal chilled water to yield [2,2′]bipyrimidinyl-5-carboxylic acid (59%). MS: 203 (M+H); 1H NMR (300 MHz, CDCl3): δ=7.71 (t, 1H), 9.06 (d, 2H), 9.40 (s, 2H).

Provenance & Evidence