Water → 2-Cyano-5-fluoropyridine

Temperature

65 °C

2-Bromo-5-fluoropyridine (recrystallized from 0.3 volumes of pentane, 1240 g, 1 equivalent) was dissolved in dimethylacetamide (2 volumes), the mixture was heated to 60-70° C. and cuprous cyanide (0.4 equivalents) was added in one portion, giving a dark green solution. Heating was continued and potassium cyanide (1.2 equivalents) was added in portions above 90° C. After completion of the addition, the resulting brown suspension was heated to 145° C. for 5 hours. The reaction mixture was allowed to cool to room temperature and poured into cold water (14 volumes). Ethylene diamine (1.2 equivalents) was added and the solution extracted with methyl t-butyl ether (4×5 volumes). The combined extracts were dried filtered and evaporated in vacuo with a bath temperature no higher than 45° C. The crude solid was purified by silica pad chromatography (5 w/w silica; 10-33% methyl t-butyl ether in 40/60 petroleum ether). Product containing fractions were evaporated to give a white crystalline solid. Mp 40-41° C., 541 g, 62.9% theory.

1. customgiving a dark green solution
2. temperatureHeating
3. additionAfter completion of the addition
4. temperaturethe resulting brown suspension was heated to 145° C. for 5 hours
5. temperatureto cool to room temperature
6. extractionthe solution extracted with methyl t-butyl ether (4×5 volumes)
7. customThe combined extracts were dried
8. filtrationfiltered
9. customevaporated in vacuo with a bath temperature no higher than 45° C
10. customThe crude solid was purified by silica pad chromatography (5 w/w silica; 10-33% methyl t-butyl ether in 40/60 petroleum ether)
11. additionProduct containing fractions
12. customwere evaporated
13. customto give a white crystalline solid

ORD record

ord-302a8426391e4367b80377bd9b2c9481

Source dataset

uspto-grants-2012_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08114989B2