3-Methylpyridine-2-carboxylic acid, also known as 3-methylpicolinic acid (3-MepicH), is a 3-substituted picolinic acid. The dianion formed by reacting 3-MepicH with lithium diisopropylamide (LDA) can undergo C-alkylation with 3-chlorobenzyl chloride.
Synthesis of II-1-2:3-methylpyridine carboxylic acid
2.00 g (19 mmol) of 2-cyano-3-methylpyridine was dissolved in 90% sulfuric acid and the resulting solution was heated and stirred at 120°C for 2 hours. After completion of the reaction, the reaction solution was cooled to 20 °C to 25 °C and a solution of 4.00 g of sodium sulfite dissolved in 8 ml of water was slowly added dropwise. After the dropwise addition was completed, the reaction mixture was continued to be stirred at the same temperature for 1.5 hours, and then warmed up to 75°C-85°C and kept for 1.5 hours. After the reaction solution was cooled, the pH was adjusted to about 3 with sodium carbonate and extracted with chloroform. The organic phases were combined, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give 1.38 g of solid product. The solid was purified by solvent recrystallization from a mixture of ethyl acetate-hexane to give the final pure product (54.0% yield). The melting point of the product was 115.5°-116.5°C and IR (KBr) showed characteristic absorption peaks: 3350, 1650, 1590 cm-1 .
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