tert-Butyl 4-(4-hydroxypyridin-2-yl)piperazine-1-carboxylate synthesis

Yield:1453265-70-7 44%

Reaction Conditions:

in butan-1-ol at 140; for 72 h;

Steps:

3.A

Step A: To a solution of 2-chloro-4-hydroxypyridine (12.9 g, 100 mmol) in n-BuOH (50 mL) was added t-butyl piperazine-l-carboxylate (46.5 g, 250 mmol). The mixture was heated at 140 °C for 3 days and then diluted with EtOAc (2 L) at ambient temperature. The organic phase was washed with saturated NH₄C1 solution and then brine. The organic layer was separated, dried over MgSC^, and concentrated under reduced pressure. The residue was purified by column chromatography (5%-20% MeOH/CH₂Cl₂) to give 12.2 g (44%) of i-butyl 4- (4-hydroxypyridin-2-yl)piperazine-l-carboxylate as a white solid. MS m/z 280.2 [M+H]⁺; 1H NMR (500 MHz, CDC1₃) δ (ppm) 7.72 (1H, d, J= 6.62 Hz), 6.20 (1H, dd, J= 6.31, 2.21 Hz), 6.02 (1H, d, J= 1.89 Hz), 3.56 (4H, m), 3.42 (4H, m), 1.50 (9H, s).

References:

WO2013/130689,2013,A1 Location in patent:Paragraph 00917; 00918