5-Chloropyridine-3-carboxylic acid methyl ester

To a stirred solution of 5-chloronicotinic acid (LV, 5 g; 31.8 mmol) in methanol (40 ml) was added sulfuric acid (4 ml). The reaction mixture was heated at 75°C for 12 h. The reaction mixture was cooled, concentrated under reduced pressure and diluted with water. The aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with sodium bicarbonate, brine, dried over Na2504, filtered and concentrated under vacuum to affordmethyl 5-chloronicotinate as a white solid (LVI; 4.4 g, 80percent yield). ‘H NMR (400 MHz, CDC13): ö 9.08 (d, J = 1.6 Hz, 1H), 8.73 (d, J = 2.4 Hz, 1H), 8.28-8.27 (t, J = 2.0 Hz, 1H), 3.96 (s, 3H). MS (M+1): 172.12To a solution of 5-chloro-nicotinic acid (20.0 g, 127 mmol, purchased from Matrix Scientific, Columbia, S.C., USA) in methanol (200 mL) at 0° C. was added thionyl chloride (18.6 mL, 255 mmol). The reaction mixture was refluxed for 4 hours. After cooling to room temperature the mixture was diluted with saturated aqueous sodium bicarbonate, extracted with AcOEt (3×300 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure to afford crude 5-chloro-nicotinic acid methyl ester (17.2 g, 79percent). 5-Chloronicotinic acid (200 mg, 1.269 mmol) was refluxed overnight in the presence of concentrated sulfuric acid (8.20 mg, 0.063 mmol) in methanol (10 ml_) at 70 °C. The reaction was monitored by TLC. After completion of the reaction, the solvent was removed by vacuum and the compound was purified by column chromatography affording the title compound (120 mg). H NMR (400 MHz, CDCI[0344j Methyl 5-chloronicotinate, Example 3.38. To a suspension of 5- chloronicotinic acid (0.68 mL, 6.35 mmol) in MeOH (8 mL) was added thionyl chloride (1.5 mL, 20.55 mmol) at 0 °C dropwise. The resulting mixture was heated at reflux for 24 h. The mixture was concentrated and 50 mL of saturated aqueous sodium bicarbonate solution was added to the residue. The resulting mixture was extracted with EtOAc (4 x 50 mL). The combined extracts were washed with sodium bicarbonate solution, water, and brine, and then dried with anhydrous sodium sulfate. The drying agent was removed by filtration and washed with EtOAc. The filtrate was concentrated in vacuo and dried to give the title compound (3.38, 698 mg). ‘H NMR (400 MHz, CDC13) 9.80 (d, J 1.7 Hz, 1H), 8.73 (d, J= 2.4 Hz, 1H), 8.27 (dd, J= 2.4, 2.4 Hz, 1H), 3.96 (s, 3H).

Molecular Weight:171.58
XLogP3:1.3
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:171.0087061
Monoisotopic Mass:171.0087061
Topological Polar Surface Area:39.2
Heavy Atom Count:11
Complexity:151
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes