2-Chloro-3-pyridineacetonitrile

(1-oxypyridin-3-yl)acetonitrile (7.5 g, 35.9 mmol) is carefully added to vigorously stirred phosphorous oxychloride (100 mL). The mixture is slowly heated to 80° C. (in 5° C. increments) over 1.5 hr. (CAUTION. If heating is too quick, violent decomposition occurs at ca 70° C.) All the solids dissolved. The reaction is heated at reflux for 3 hr. The excess phosphorous oxychloride is removed and the residue is cautiously treated with cold water. Saturated sodium bicarbonate is added to make the mixture basic, then it is extracted with ethyl acetate (3.x.). The combined extract is washed with brine, dried, filtered and concentrated. The residue is purified by chromatography eluting with pentane-10 to 100percent ether. The second compound off the column is the desired (2-chloropyridin-3-yl)acetonitrile (2.35 g, 42.9percent yield) a light brown solid.(1-Oxypyridin-3-yl)acetonitrile (1115) (4.00 g, 29.8 mmol) was added slowly to a stirred solution of POCI(Step 3) INTERMEDIATE 2(2-Chloropyridin-3-yl)acetonitrileIn a 3 L reactor, set for reflux under positive nitrogen pressure and using a bleach scrubber, was prepared a solution of potassium cyanide (68.32 g, 1.04M) in EtOH (136 INTERMEDIATE 2(2-Chloro'yridin-3 - vDacetonitrileIn a 3 L reactor, set for reflux under positive nitrogen pressure and using a bleach scrubber, was prepared a solution of potassium cyanide (68.32 g, 1.04M) in EtOH (136 mL) and water (255 mL). The mixture was heated to reflux, at which point a solution of 2-chloro-3-(chloromethyl)pyridine {Intermediate 1; 170.0 g, 1.04M) in EtOH (170 mL) was added drop wise over 30 minutes. The whole mixture was maintained at reflux for a further 150 minutes. The mixture was then allowed to cool just below boiling point and the equipment set for distillation. A total of 8.5 volumes of EtOH were removed. On cooling, half a volume of water was added. At a temperature of 4O0C, the solution was seeded and crystallised instantaneously. The thick beige slurry was allowed to cool to ambient temperature and then to O0C. This mixture was filtered, rinsed with cold water (2 vols) and dried at 450C in a vacuum oven overnight. The title compound was afforded as a beige solid in excellent yield and purity (126.9 g, 80percent). 'H (d6-DMSO, 300 MHz) 8.45 (IH, dd), 8.00 (IH, dd), 7.50 (IH, dd), 4.15 (2H, s). LCMS (ES)+ RT 2.15 min, m/e 153.01 155.01 (M+l M+3, Product).In a 3 L reactor, set for reflux under positive nitrogen pressure and using a bleach scrubber, was prepared a solution of potassium cyanide (68.32 g, 1.04M) in EtOH (136 mL) and water (255 niL). The mixture was heated to reflux, at which point a solution of 2-chloro-3-(chloromethyl)pyridine {Intermediate 1; 170.0 g, 1.04M) in EtOH (170 mL) was added dropwise over 30 minutes. The whole mixture was maintained at reflux for a further 150 minutes. The mixture was then allowed to cool just below boiling point and the equipment set for distillation. A total of 8.5 volumes of EtOH were removed. On cooling, half a volume of water was added. At a temperature of 4O0C, the solution was seeded and crystallised instantaneously. The thick beige slurry was allowed to cool to ambient temperature and then to 00C. This mixture was filtered, rinsed with cold water (2 vols) and dried at 450C in a vacuum oven overnight. The title compound was afforded as a beige solid in excellent yield and purity (126.9 g, 80percent). δH (d6-DMSO, 300 MHz) 8.45 (IH, dd), 8.00 (IH, dd), 7.50 (IH, dd), 4.15 (2H, s). LCMS (ES)+ RT 2.15 min, m/e 153.01 155.01 (M+l M+3, Product).

Molecular Weight:152.58
XLogP3:1.5
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:152.0141259
Monoisotopic Mass:152.0141259
Topological Polar Surface Area:36.7
Heavy Atom Count:10
Complexity:149
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes