Synthesis
General procedure for the synthesis of 5-hydroxypyrimidine from 5-methoxypyrimidine: a mixture of 5-methoxypyrimidine (2.99 g, 27.2 mmol) and powdered potassium hydroxide (8.96 g, 85%, 136 mmol) in methanol (50 mL) was placed in a sealed tube and the reaction was heated at 150 °C overnight. Upon completion of the reaction, the mixture was cooled to room temperature, neutralized by the addition of acetic acid and subsequently concentrated under reduced pressure. The resulting residue was ground with hot acetonitrile (2 x 100 mL), the acetonitrile extracts were combined and concentrated under reduced pressure to give 7.51 g of an off-white solid. The solid was ground with hot ethyl acetate (100 mL) and the ethyl acetate extract was concentrated under reduced pressure to give 1.81 g of off-white solid. Finally, further purification by fast chromatography (silica gel as stationary phase and 9:1 dichloromethane/methanol as mobile phase) afforded the target product 5-hydroxypyrimidine (1.11 g, 43% yield) as an off-white solid. Its 1H NMR (300 MHz, DMSO-d6) data were as follows: δ 10.45 (broad single peak, 1H), 8.67 (single peak, 1H), 8.34 (single peak, 2H).
References
[1] Chemistry - A European Journal, 2003, vol. 9, # 20, p. 4997 - 5010
[2] Patent: US2006/173049, 2006, A1. Location in patent: Page/Page column 28-29
[3] Patent: WO2008/65393, 2008, A1. Location in patent: Page/Page column 30
[4] Chemistry and Industry (London, United Kingdom), 1956, p. 1453
[5] Patent: US2002/143025, 2002, A1
