Dimethylformamide → 4-Chloropyridine-3-carbaldehyde

Participants

Reaction Steps

In a flame-dried 3-necked 100 ml r.b. flask fitted with internal thermometer was prepared LDA at -78° using diisopropyl amine (2.8 ml, 19.9 mmol) and 2.5 M n-BuLi (8.32 ml, 20.8 mmol) in dry THF (15 ml). After stirring for 20 min, 4-chloropyridine (2.26 g, 19.9 mmol) in THF (5 ml) was added via a syringe pump at 0.15 ml/min over about 30 min. The mixture was stirred for 1 h, then dry DMF (4.8 ml, 62 mmol) was added via a syringe pump so that the temperature remained at -78°. After complete addition, the mixture was stirred 30 min then allowed to warm to -40° and hydrolyzed with 5% NaHCO3. The mixture was extracted twice with t-butyl methyl ether and washed with 5% NaHCO3, brine, dried (MgSO4), and concentrated. Chromatography (flash silica gel, 1:1 t-butyl methyl ether/hexanes) afforded the title compound as a white solid. (1.55 g, 55%).

Provenance & Evidence