Dimethylformamide → 4-Chloropyridine-3-carbaldehyde

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 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, dnred (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%).

1. customflask fitted with internal thermometer
2. additionwas added via a syringe pump at 0.15 ml/min over about 30 min
3. customremained at -78°
4. additionAfter complete addition
5. stirringthe mixture was stirred 30 min
6. extractionThe mixture was extracted twice with t-butyl methyl ether
7. washwashed with 5% NaHCO3, brine
8. concentrationconcentrated

ORD record

ord-1d6feaac58414540b53048083150fdc4

Source dataset

uspto-grants-1999_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05985886