tert-Butyl 4-(cyanomethyl)-4-hydroxypiperidine-1-carboxylate Chemical Properties

Boiling point:

387.1±27.0 °C(Predicted)

Density 

1.138±0.06 g/cm3(Predicted)

storage temp. 

2-8°C

pka

13.45±0.20(Predicted)

tert-Butyl 4-(cyanomethyl)-4-hydroxypiperidine-1-carboxylate Usage And Synthesis

Synthesis

Under nitrogen protection, n-butyllithium (2.5 M hexane solution, 12 mL, 30.1 mmol) was slowly added dropwise to a pre-cooled solution of diisopropylamine (3.05 g, 30.1 mmol) in tetrahydrofuran (25 mL) at 0 °C. The reaction mixture was stirred at room temperature for 30 minutes and then cooled to -78°C. A tetrahydrofuran solution of acetonitrile (1.24 g, 30.2 mmol) was added dropwise to the reaction system at -78 °C and stirring was continued for 1 hour. Subsequently, a tetrahydrofuran (12 mL) solution of tert-butyl 4-oxopiperidine-1-carboxylate (3.0 g, 15.1 mmol) was added. The reaction mixture was warmed to room temperature and stirred for 1 hour. Upon completion of the reaction, the reaction was quenched with saturated aqueous ammonium chloride solution (100 mL) and extracted with ethyl acetate. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (eluent: petroleum ether/ethyl acetate = 100:0 to 80:20) to afford N-tert-butyloxycarbonyl-4-hydroxy-4-carbonitrilemethylpiperidine (1.5 g, 41% yield) as a white solid.LC-MS (ESI): m/z [M + H]+ calculated value 241.

References

[1] Patent: WO2014/210354, 2014, A1. Location in patent: Page/Page column 140
[2] Patent: WO2017/60874, 2017, A1. Location in patent: Paragraph 00618-00619
[3] Patent: US2017/101406, 2017, A1. Location in patent: Paragraph 1662; 1663

tert-Butyl 4-(cyanomethyl)-4-hydroxypiperidine-1-carboxylate(774609-73-3)Related Product Information

• tert-Butyl 4-(cyanomethyl)-4-hydroxypiperidine-1-carboxylate
• (1-BOC-piperidin-4-yl)acetonitrile