Synthesis
Synthesis of methyl 2-chloro-3-methylisonicotinate (6): In a 200 mL solution of 2-chloro-3-methylisonicotinic acid 5 (116.56 mmol) and potassium carbonate (233.12 mmol) in dimethyl formamide (DMF), 174.84 mmol of methyl iodide was added under stirring conditions at RT. Continued to stir the mixture for another 16 h at RT. Ice-cold water (1 L) was added to the reaction mixture after it was finished, and two 100 mm of ethyl acetate were used for extraction. Crude was gathered by washing the combined organic layer with 400 mL of brine, drying it over anhydrous Na₂SO₄, and then concentrating it under reduced pressure. The raw material was refined by the use of column chromatography using a silica gel (100-200) mesh eluted with 10-15% ethyl acetate in n-hexane. The isolated molecule was then concentrated under decreased pressure to produce 3-Methylisonicotinate methyl 2-chloride 6. Yield 93.38% as a colourless liquid. R_f = 0.4 (10% ethyl acetate in n-hexane). ¹H NMR (400 MHz, CDCl₃): δ 8.33-8.31 (dd, J = 0.4Hz, 5.2Hz, 1H), 7.53 (d, J = 4.8Hz, 1H), 3.96 (t, J = 2 Hz, 10.4HHz, 2H), 2.59 (s, 3H); EI-MS: m/z (M+H) 186.14 [1].
References
[1] Modugu, Narender Reddy & Nimmareddy, Rajashekar Reddy & Maiti, Bhimcharan & Ega, Jagadish. (2024). Design and Synthesis of Some Novel 1-chloro-6-(4-(sulfonyl) piperidin-4-yl) phenyl)-6,7-dihydro-5H-cyclopenta[c]pyridin-5-ones as In Vitro Anticancer Agents. Indian Journal of Chemistry. 63. 701-708.
https://doi.org/10.56042/ijc.v63i7.7677
