Diethyl (cyanomethyl)phosphonate → tert-Butyl 4-(cyanomethylidene)piperidine-1-carboxylate

Temperature

0 °C

To a three necked round bottom flask equipped with a mechanical stirring bar was added potassium tert-butoxide (263 mL, 263 mmol, 1.0 M in THF) and THF (200 mL). The mixture was cooled to 0° C., followed by the addition of diethyl (cyanomethyl)phosphonate (43.7 mL, 276 mmol) slowly by syringe. The reaction mixture was maintained at 0° C. for 10 minutes, then warmed to ambient temperature and maintained for 1 hour. The mixture was cooled to 0° C. and treated with the dropwise addition of tert-butyl 4-oxopiperidine-1-carboxylate (50.0 g, 251 mmol) in THF (150 mL) over 30 minutes. After addition, the mixture was maintained at 0° C. for 20 minutes, then warmed to ambient temperature and maintained for 18 hours. The reaction mixture was then diluted with water (800 mL) and extracted with EtOAc (700 mL×2). The combined organic extracts were washed with water, brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to afford the title compound as a light pink solid.

1. customTo a three necked round bottom flask equipped with a mechanical stirring bar
2. temperatureThe reaction mixture was maintained at 0° C. for 10 minutes
3. temperaturewarmed to ambient temperature
4. temperaturemaintained for 1 hour
5. temperatureThe mixture was cooled to 0° C.
6. additionAfter addition
7. temperaturethe mixture was maintained at 0° C. for 20 minutes
8. temperaturewarmed to ambient temperature
9. temperaturemaintained for 18 hours
10. extractionextracted with EtOAc (700 mL×2)
11. washThe combined organic extracts were washed with water, brine
12. dry with materialdried over anhydrous Na2SO4
13. filtrationfiltered
14. concentrationconcentrated in vacuo

ORD record

ord-6e4efa82178b4ce3848266069b67292b

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09328099B2