Dimethylacetamide → 6-Chloro-2-methylpyrimidine-4-carbonitrile

The 4,6-dichloro-2-methyl-pyrimidine (10 g, 60 mmol), palladium (II) trifluoroacetate (0.86 g, 2.6 mmol), zinc dust (65.3 g, 11.4 mmol), rac-2-(di-t-butylphosphino)-1,1-binaphthyl (2.1 g, 5.3 mmol), zinc cyanide (3.95 g, 33.7 mmol) and dimethyl acetamide (316 ml) were added to a 500 mL, flame-dried flask. The vessel was evacuated and back-filled with N2 (3×). The mixture was stirred under N2 for 30 min. at RT, then heated to 95° C. After 2.5 hours the mixture was diluted with EtOAc (300mL), and washed with water (300 mL×3). The organic fractions were combined, dried over MgSO4, filtered, and the volatiles removed in vacuum. The residue was dissolved in EtOAc (100 mL), washed with water (50 ml), and the layers separated. The aqueous phase was then extracted with EtOAc (50 mL), the organic fractions combined, dried over MgSO4, filtered, and the volatiles removed in vacuum. The crude mixture was purified by chromatography on silica gel (eluting 1:19 ethyl acetate:hexane) to yield the titled compound as a colorless oil. 1H NMR (CD3OD): 8.235 (s, 1H), 2.816 (s, 3H).

1. customflame-dried flask
2. customThe vessel was evacuated
3. additionback-filled with N2 (3×)
4. temperatureheated to 95° C
5. additionAfter 2.5 hours the mixture was diluted with EtOAc (300mL)
6. washwashed with water (300 mL×3)
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. customthe volatiles removed in vacuum
10. dissolutionThe residue was dissolved in EtOAc (100 mL)
11. washwashed with water (50 ml)
12. customthe layers separated
13. extractionThe aqueous phase was then extracted with EtOAc (50 mL)
14. dry with materialdried over MgSO4
15. filtrationfiltered
16. customthe volatiles removed in vacuum
17. customThe crude mixture was purified by chromatography on silica gel (eluting 1:19 ethyl acetate:hexane)

ORD record

ord-2fbb066f76f84791a5f135b332225a42

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08552022B2