Extracurricular laboratory: Synthetic route of 5-Chloro-3-methylpyridine-2-carboxylic acid

With the rapid development of chemical substances, we look forward to future research findings about 886365-46-4.

The major producers of chemicals have been the Europe, Japan and China. Due to the growing call for a cleaner, greener environment, people will have to find innovative ways to maintain their relevance. Here is a compound 886365-46-4, name is 5-Chloro-3-methylpyridine-2-carboxylic acid. This compound has unique chemical properties. The synthetic route is as follows. SDS of cas: 886365-46-4

To a solution of Intermediate 12 (100 mg, 0.195 mmol) in N,N-dimethylformamide (1.0 mL) was added 5-chloro-3-methylpicolinic acid (43.6 mg, 0.254 mmol), (O-(7-azabenzotriazol-1-yl)-N,N,N?,N?-tetramethyluronium hexafluorophosphate) (111 mg, 0.293 mmol), and pyridine (0.047 mL, 0.586 mmol). The reaction was stirred at ambient temperature for 2 hours, and then partitioned between water and ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was redissolved in DCM (0.5 mL) and TFA (0.301 mL, 3.91 mmol) was added. The reaction was stirred at RT for an hour. The reaction was quenched with saturated aqueous sodium carbonate, and partitioned between water and ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by silica-gel column chromatography, eluting with 0-50% (3:1 ethyl acetate:ethanol, 2% ammonium hydroxide) in heptanes, to provide the title compound (62 mg, 68.2% yield). 1H NMR (400 MHz, DMSO-d6) ppm 1.28-1.34 (m, 1H) 1.46 (s, 3H) 1.68-1.72 (m, 1H) 1.74 (s, 3H) 1.87-2.09 (m, 2H) 2.57 (s, 3H) 3.68 (d, J=5.77 Hz, 1H) 6.03 (br. s., 2H) 7.17 (dd, J=11.74, 8.90 Hz, 1H) 7.72-7.81 (m, 1H) 7.81-7.89 (m, 1H) 8.03 (dd, J=2.25, 0.68 Hz, 1H) 8.52-8.61 (m, 1H) 10.54 (s, 1H). LC/MS (ESI+) m/z=465.1 (M+H).

With the rapid development of chemical substances, we look forward to future research findings about 886365-46-4.

Reference:
Patent; LEWIS, Richard T.; ALLEN, Jennifer R.; BROWN, James; GUZMAN-PEREZ, Angel; HUA, Zihao; JUDD, Ted; LIU, Qingyian; OLIVIERI, Philip R.; ROMERO, Karina; SCHENKEL, Laurie; STELLWAGEN, John; WHITE, Ryan; US2015/38497; (2015); A1;,
Pyridine – Wikipedia,
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