Diethyl (cyanomethyl)phosphonate → 2-(1,1-dioxidodihydro-2H-thiopyran-4(3H)-ylidene)acetonitrile

Temperature

0 °C

Potassium tert-butoxide (3.5 mL, 3.5 mmol, 1.0 M in THF) was stirred at 0° C. and THF (8 mL) was added. Diethyl (cyanomethyl)phosphonate (0.56 mL, 3.5 mmol) was added 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 dihydro-2H-thiopyran-4(3H)-one 1,1-dioxide (0.50 g, 3.4 mmol) in THF (5 mL). 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 and extracted with EtOAc. The combined organic extracts were washed with water, brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The residue was purified MPLC on silica gel (using a gradient elution of 0-50% EtOAc/hexanes). Desired fractions were identified, combined, and concentrated in vacuo to the title compound.

1. temperaturewarmed to ambient temperature
2. temperaturemaintained for 1 hour
3. temperatureThe mixture was cooled to 0° C.
4. additionAfter addition
5. temperaturethe mixture was maintained at 0° C. for 20 minutes
6. temperaturewarmed to ambient temperature
7. temperaturemaintained for 18 hours
8. extractionextracted with EtOAc
9. washThe combined organic extracts were washed with water, brine
10. dry with materialdried over anhydrous Na2SO4
11. filtrationfiltered
12. concentrationconcentrated in vacuo
13. customThe residue was purified MPLC on silica gel (
14. washa gradient elution of 0-50% EtOAc/hexanes)
15. concentrationconcentrated in vacuo to the title compound

ORD record

ord-a5da932b56974f3a85d5fb9b8a753211

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09328099B2