Ethyl 4-pyrimidinecarboxylate

31462-59-6

64-17-5

62846-82-6

General procedure for the synthesis of ethyl 4-pyrimidinecarboxylate from pyrimidine-4-carboxylic acid and ethanol: Thionyl chloride (3.55 mL, 48.4 mmol, 3 eq.) was slowly added dropwise to a solution of pyrimidine-4-carboxylic acid (2 g, 16.1 mmol) in anhydrous ethanol (15 mL). The reaction mixture was heated to reflux for 14 hours. Upon completion of the reaction, the mixture was cooled to room temperature and the pH was adjusted with saturated aqueous sodium bicarbonate solution to 8. Subsequently, the reaction mixture was extracted with ethyl acetate (4 x 50 mL). The organic phases were combined, washed with brine (30 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give Intermediate 23 (1.7 g, 77% yield). The product was confirmed by 1H NMR (DMSO-d6): δ 9.40 (d, J = 1.0 Hz, 1H), 9.10 (d, J = 5.1 Hz, 1H), 8.05 (dd, J = 5.1, 1.3 Hz, 1H), 4.39 (q, J = 7.1 Hz, 2H), 1.35 (t, J = 7.1 Hz, 3H); mass spectrum (MS): m/ z 153 [M + H]+; thin layer chromatography (TLC) conditions: 40% hexane/ethyl acetate, Rf = 0.40.