Water → 2-Cyano-5-fluoropyridine

Participants

Reaction Conditions

Reaction Steps

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.

Provenance & Evidence