Diisopropylamine → HCID 86694136, compound

Participants

Reaction Steps

Diisopropylamine (0.9 mL, 6.42 mmol) and lithium chloride (0.120 g, 2.83 mmol) were dissolved in dry tetrahydrofuran (1 mL) under nitrogen and cooled in a dry ice bath. A solution of butyllithium (2.5 M in hexanes, 2.6 mL, 6.50 mmol) was added slowly and the reaction stirred for 10 minutes. 2-Fluoropyridine (0.5 mL, 5.81 mmol) was added dropwise and the mixture stirred for 1 hour. Cyclopropanecarboxaldehyde (0.5 mL, 6.69 mmol) was added slowly. After 30 minutes, the mixture was quenched by addition of saturated ammonium chloride (5 mL). Water (200 mL) and ethyl acetate (300 mL) were added and the phases mixed and separated. The organic was dried with magnesium sulfate and evaporated to dryness under reduced pressure. Purification using silica chromatography (hexane to ethyl acetate gradient) gave cyclopropyl(2-fluoropyridin-3-yl)methanol (0.415 g, 2.482 mmol, 42.7% yield). The alcohol was dissolved in chloroform (150 mL) and treated with manganese (IV) oxide (3.0 g, 34.5 mmol). The suspension was heated at gentle reflux for 14 hours. The crude product was purified using silica chromatography (hexane to ethyl acetate gradient) to give cyclopropyl(2-fluoropyridin-3-yl)methanone (0.270 g, 1.635 mmol, 28.1% yield) as a clear oil.

Provenance & Evidence