Ethylene Oxide → 4-Pyridineethanol,3-fluoro-(9CI)

Participants

Reaction Conditions

Reaction Steps

n-Butyl lithium (1.8 M in hexanes, 35 mL, 64.4 mmol) was charged to a round bottom flask and diluted with THF (25 mL). The solution was cooled to 0° C., and a solution of N,N-diisopropylamine (9.0 mL, 65 mmol) in THF (25 mL) was slowly added. The mixture was stirred at 0° C. for 20 min and was cooled to −78° C. A solution of 3-fluoropyridine (20 g, 206 mmol) was added dropwise (temperature of mixture kept below −70° C.), resulting in the formation of a red precipitate. The mixture was stirred at −78° C. for 4 h. Ethylene oxide (4.6 M in THF, 67.2 mL, 309 mmol) was slowly added, and the mixture allowed to warm to room temperature overnight. The mixture was diluted with water and CH2Cl2. The layers were separated, and the water layer extracted with CH2Cl2. The organic layers were combined, washed with brine, dried (Na2SO4), filtered, and concentrated to provide a dark brown oil. The residue was purified by chromatography (SiO2, 19:1-6:1 CH2Cl2:CMA) to provide 3-fluoro-4-(2-hydroxyethyl)pyridine (6.7 g, 23%) as a tan oil.

Provenance & Evidence