N,N-Di(propan-2-yl)methaniminium chloride → 4-Chloro-6-ethenyl-5-fluoropyrimidine

To a solution of N-isopropyl-N-methylenepropan-2-aminium chloride (13.3 g, 88.7 mmol) in acetonitrile (55 mL) was added 4-chloro-5-fluoro-6-methylpyrimidine (10.0 g, 68.2 mmol). The reaction flask was flushed with argon and the mixture was heated at reflux for 24 hours with stirring, then cooled to room temperature. Water (130 mL) was added and the mixture was extracted with dichloromethane (140 mL). The organic phase was washed with 10% aqueous KHSO4 (400 mL) and dried over Na2SO4. The solution was filtered and evaporated in vacuo at 300 millibar pressure and 35° C. tert-Butylcatechol (30 mg, 0.2 wt %, based on the mass of the crude material) was added. Residual solvent was removed under vacuum at 50° C. and the crude product was then distilled at 5 millibar pressure and 50° C. (oil bath). tert-Butylcatechol (0.1 wt %) was added to the distilled 4-chloro-5-fluoro-6-vinyl pyrimidine (7.9 g, 73%) which was obtained as a slightly yellow oil.

1. customThe reaction flask was flushed with argon
2. temperaturethe mixture was heated
3. temperatureat reflux for 24 hours
4. additionWater (130 mL) was added
5. extractionthe mixture was extracted with dichloromethane (140 mL)
6. washThe organic phase was washed with 10% aqueous KHSO4 (400 mL)
7. dry with materialdried over Na2SO4
8. filtrationThe solution was filtered
9. customevaporated in vacuo at 300 millibar pressure and 35° C. tert-Butylcatechol (30 mg, 0.2 wt %
10. additionwas added
11. customResidual solvent was removed under vacuum at 50° C.
12. distillationthe crude product was then distilled at 5 millibar pressure and 50° C. (oil bath)
13. additiontert-Butylcatechol (0.1 wt %) was added to the distilled 4-chloro-5-fluoro-6-vinyl pyrimidine (7.9 g, 73%) which
14. customwas obtained as a slightly yellow oil

ORD record

ord-6a7d387eb67a4352a59362016c9631e2

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09388167B2