4-Chloroquinoline → Quinoline, 4-ethyl-

Participants

Reaction Steps

Ethyltriphenylphosphonium bromide (45.0 g, 0.122 m) was suspended in anhydrous dimethoxyethane under a nitrogen atmosphere and cooled to -30° C. n-Butyllithium (12.2 mL of a 1 molar solution in THF) was added and the reaction mixture was stirred at -30° to -40° C. for 1 hour. 4-Chloroquinoline (9.0 g, 0.055 m) was added and the suspension was slowly warmed to room temperature and allowed to stir overnight. After heating under reflux for 2-3 hours, 50-100 mL of solvent was distilled out and replaced by a solution of sodium carbonate (12.9 g) in water (60-80 mL). After refluxing for another 2-3 hours, the solvents were evaporated and the residue was partitioned between methylene chloride and aqueous HCl. The organic phase was extracted twice with HCl, and the combined aqueous phases were basified with sodium hydroxide (50:50) to pH 9-10, extracted with ether, dried, and evaporated to give an oil which was purified by HPLC on silica gel eluting with 1:1 ethyl acetate:hexane to give 5.54 g (64%) of 4-ethylquinoline.

Provenance & Evidence