3-Chloro-4-cyanopyridine

Pale Yellow Solid

To a stirred solution of 2, 2, 6, 6-tetramethyl piperidine (17.16 mL, 100.854 mmol) in THF (100 mL) was added n-BuLi (2.17 M, 44.26 mL, 96.052 mmol) at -30°C. After stirring the mixture for 15 mm at 25°C, it was cooled to -78°C and 4-cyanopyridine (5 g, 48.026 mmol) in THF (40 mL) was added dropwise. After stirring the reaction mixture for 30 mm at -78°C, hexachioroethane (23.87 g, 100.854 mmol) in THF (50 mL) was added at -78°C. The resulting mixture was stirred for 30 mm at -78°C and was quenched with saturated NH4C1 solution. Water (100 mL) was added to the reaction mixture and extracted with ethyl acetate (4 x 300 mL). The combined organic layer was dried over anhydrous sodium sulfate, concentrated under reduced pressure to afford the crude material which was purified by column chromatography using silica (100-200 mesh) and 5percent EtOAc-hexane as eluent to afford 3-chloropyridine-4-carbonitrile (3.5 g, 25.26 1 mmol, 53percent) as pale white solid. GCMS: 138 (mlz).Preparation 71 Step A: Preparation of 3-chloroisonicotinonitrile: In a 4 neck 3L round bottom flask equipped with mechanical stirrer and condenser, was added 4-cyanopyridine-n- oxide (50 g, 416 mmol), phosphoryl trichloride (153 ml, 1665 mmol), and phosphorous pentachloride(121 g, 583 mmol). The reaction was stirred at 105 Example 205 (Representative Example) 3-(2-chloropyridm-4-yloxy)isomcotinonitrile[00586] Step A: Preparation of 3-chloroisonicotinoiiitrile: In a 4 neck 3L round bottom flask equipped with mechanical stirrer and condenser, was added 4-cyanopyridine-n-oxide (50 g, 416 mmol), phosphoryl trichloride (153 ml, 1665 mmol). and phosphorous pentachloride(121 gExample 25.1 : 3-Chloro-isonicotinonitrile. A mixture of 1 -oxy-isonicotinonitrile (5.0 g, 0.042 mol), phosphorus pentachloride (12.0 g, 0.059 mol) and phosphorus oxychloridc (20 mL) was heated at 120-130° C for 2 hours. The reaction mixture was cooled, poured into ice and neutralized by the addition of solid sodium bicarbonate. The mixture was extracted with diethyl ether and the combined organic layer was dried over sodium sulfate, filtered and concentrated. The residue was purified on silica gel to give 3-chloro-isonicotinonitrile (1.2 g, 21 percent).

Molecular Weight:138.55
XLogP3:1.1
Hydrogen Bond Acceptor Count:2
Exact Mass:137.9984758
Monoisotopic Mass:137.9984758
Topological Polar Surface Area:36.7
Heavy Atom Count:9
Complexity:137
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes