4,6-Dichloro-5-methoxypyrimidine → Isopropyl 4-[(6-chloro-5-methoxypyrimidin-4-yl)oxy]piperidine-1-carboxylate

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Reaction Steps

To a solution of 4-hydroxy-piperidine-1-carboxylic acid isopropyl ester (3.15 g, 17 mmol) and 4,6-dichloro-5-methoxy-pyrimidine (3.00 mg, 17 mmol) in 15 ml of THF, IM potassium-t-butoxide in THF (18.4 ml, 18.4 mmol) was added dropwise at 0° C. After 45 min, the crude mixture was extracted with CH2Cl2 and brine. Organic phase was dried over MgSO4, filtered, and concentrated. The residue was purified by column chromatography on silica gel with hexane/ethyl acetate (3:1→1:1 v/v) to provide 4-(6-chloro-5-methoxy-pyrimidin-4-yloxy)-piperidine-1-carboxylic acid isopropyl ester as a solid (4.7 g, 85%). 1HNMR (CDCl3, 400 MHz) δ 1.24-1.28 (d, 6H), 1.80-1.84 (m, 2H), 2.00-2.05 (m, 2H), 3.37-3.44 (m, 2H), 3.77-3.81 (m, 2H), 3.91 (s, 3H), 4.92-4.95 (m, 1H), 5.38-5.40 (m, 1H), 8.27 (s, 1H). Exact mass calculated for C14H20ClN3O4 329.11. found 330.1 (MH+).

Provenance & Evidence