4-Piperidinol, 1-(5-methyl-2-pyrimidinyl)- synthesis

Yield:1236285-21-4 65%

Reaction Conditions:

with triethylamine in N,N-dimethyl-formamide at 100; for 5 h;

Steps:

6

4-Hydroxy-piperidine (2.0 g, 19.8 mmol), 2-chloro-5-methyl-pyrimidine (2.8 g, 19.38 mmol) and triethylamine (5.5 mL, 39.5 mmol) were dissolved in dimethylformamide (100 mL). The temperature was elevated to 100 °C and the mixture was stirred for 5 hours. The temperature was changed to room temperature, and water and ethyl acetate were added thereto. The mixture was extracted with ethyl acetate (100 mL) three times, concentrated by distilling under reduced pressure, and separated by column chromatography using 3:1 mixture solution of ethyl acetate and hexane to obtain 1-(5-methyl-pyrimidin-2-yl)-piperidin-4-ol (2.5 g, 65% yield). 1-(5-Methyl-pyrimidin-2-yl)-piperidin-4-ol (2.5 g, 12.9 mmol) was then reacted according to the method of Preparation Example 4 to obtain the title compound (2.2 g, 82% yield).[341] NMR: ¹H-NMR(CDCl₃) 8.15(2H, s), 5.33(2H, s), 4.32~4.22(2H, m), 3.83~3.74(1H, m), 3.37~3.27(2H, m), 2.11(3H, s), 2.03~1.94(2H, m), 1.62~1.50(2H, m)

References:

WO2012/111995,2012,A1 Location in patent:Page/Page column 26-27