N,N-Diethylaniline → 4-Chloro-2-(methylthio)pyrimidine-5-carboxylic acid ethyl ester

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Reaction Steps

A mixture of 4-hydroxy-2-(methylsulfanyl)pyrimidine-5-carboxylic acid ethyl ester (50 g, 0.234 mmol), POCl3 (110 mL, 1.17 mmol) and diethylaniline (70 mL, 0.28 mmol) was refluxed for 5 h. The solvent was removed under vacuum and the residue was dissolved in ice H2O and cautiously neutralized with aqueous NaHCO3. After extraction with EtOAc (3×400 mL), the organic extracts were combined, dried and concentrated to give 4-chloro-2-(methylsulfanyl)pyrimidine-5-carboxylic acid ethyl ester as a yellow solid (42 g, 77% yield). 1H NMR (300 MHz, CDCl3): δ 8.92 (s, 1H), 4.41 (q, J=7.2 Hz, 2H), 1.40 (t, J=7.2 Hz, 3H).

Provenance & Evidence