Phosphorus oxychloride → 4-Chloro-6-(methoxymethyl)pyrimidine

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Reaction Steps

6-(Methoxymethyl)pyrimidin-4-ol (1.38 g, 9.85 mmol) was taken up in dichloromethane (14 ml) and phosphorous oxychloride (9 mL, 97 mmol) was added at ambient temperature. The mixture was stirred at ambient for 18 h and concentrated. The residue was taken up in ice-water and the pH was adjusted to 7 with 1N sodium hydroxide. The mixture was extracted with chloroform and dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography (5-10% ethyl acetate/chloroform) to afford 4-chloro-6-(methoxymethyl)pyrimidine (1.2 g, 7.57 mmol, 77% yield) as a pale yellow oil, which solidified on standing. 1H NMR (400 MHz, CDCl3) δ ppm 8.88 (1 H, d, J=1.01 Hz), 7.52 (1 H, d, J=1.01 Hz), 4.53 (2 H, s), 3.50 (3 H, s). MS (LC/MS) R.T.=0.98; [M+H]+=159.10.

Provenance & Evidence