2-Chloro-4-(difluoromethyl)pyridine

Preparation of 2-chloro-4-(difluoromethyl)pyridine 2-Chloropyridine-4-carbaldehyde (990mg, 7.0mM) was dissolved in dichloromethane (40ml_) with stirring and the solution cooled to 0-5°C. Diethylamino sulfurtrifluoride (2.82g, 2.31 ml, 17.5mM) was added drop-wise over 15 minutes, keeping the reaction temperature below 5°C. The solution was stirred in the cold for 2 hours, allowed to warm slowly to room temperature and stood overnight. The reaction mixture was gradually added to saturated sodium hydrogen carbonate solution (30ml_) and ice (100ml_), making sure that the pH of the solution was >7 at all times. After 30 minutes the mixture was diluted with dichloromethane (30ml_) and water (20ml_) and the organic phase separated. The aqueous phase was further extracted with dichloromethane (2 x 20ml_). The organic extracts were combined, washed with water, dried over magnesium sulfate, filtered and the filtrate evaporated giving a yellow liquid which was chromatographed to give 2- chloro-4-(difluoromethyl)pyridine as a colourless liquid (813mg, 71 percent) H NMR (CDCI2-Chloropyridine-4-carbaldehyde (990mg, 7.0mM) was dissolved in dichloromethane (4OmL) with stirring and the solution cooled to 0-5°C. Diethylamino sulfurtrifluoride (2.82g, 2.31 ml, 17.5mM)was added drop-wise over 15 minutes, keeping the reaction temperature below 5°C. The solution was stirred in the cold for 2 hours, allowed to warm slowly to room temperature and stood overnight. The reaction mixture was gradually added to saturated sodium hydrogen carbonate solution (3OmL) and ice (lOOmL), making sure that the pH of the solution was >7 at all times. After 30 minutes the mixture was diluted with dichloromethane (3OmL) and water (2OmL) and theorganic phase separated. The aqueous phase was further extracted with dichloromethane (2 x2OmL). The organic extracts were combined, washed with water, dried over magnesium sulfate, filtered and the filtrate evaporated giving a yellow liquid which was chromatographed to give 2-chloro-4-(difluoromethyl)pyridine as a colourless liquid (813mg, 71 percent)1H NMR (CDCI3): ö 8.54 (d, 1H); 7.81 (dd, 1H); 7.45 (d, 1H); 6.71 (t, 1H)DAST (20.53 mL, 155.42 mmol) was added dropwise to 2-chloroisonicotinaldehyde (10 g, 70.64 mmol) in DCM (150 mL) at 0°C over a period of 10 minutes under nitrogen. The temperature was increased to room temperature and stirred for 12 hours. The reaction mixture was quenched and adjusted to pH 7-8 with saturated NaHC0

Molecular Weight:163.55
XLogP3:2.4
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:163.0000331
Monoisotopic Mass:163.0000331
Topological Polar Surface Area:12.9
Heavy Atom Count:10
Complexity:110
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes