Methyl 2-methylnicotinate

Light Brown Oil

A mixture of 3-bromo-2-methylpyridine (5.0 g, 29.0 mmol), Pd(dppf)C12 (2.1 g, 2.9 mmol) and Et3N (8.8 g, 87 mmol) in MeOH (250 mL) was stirred at 80 °C and 5OPsi under CO for 1 6h. Solid was then filtered out and the filtrate was concentrated. The residue was purified by column chromatography (PE:EA=5: 1) to give the desired product (4.1 g, 93.6percent). ‘H NMR (CD3OD, 400MHz) (ppm): 8.57 - 8.42 (m, 1H), 8.08 (d, 1=8.0 Hz, 1H), 7.10 (dd, 1=4.8, 7.8 Hz, 1H), 3.81 (s, 3H), 2.73 (s, 3H). LCMS (mlz): 152.0 [M+H]+General procedure: To a solution of carboxylic acid 22 or 29–31 (0.1mol) in dry methanol (150mL), concd HTo a stirred solution of Compound 21.1 (10.0 g, 66.2 mmol), m-chloroperbenzoic acid (m-CPBA) (16.3 g, 94.5 mmol) and DCM (140 mL) were added into a 250 mLflask. And stirred at room temperature for overnight, the aqueous solution of saturated sodium bicarbonate was added to adjusted pH to 7'8, the mixture was extracted with DCM (50 mL×2), the combined organic layers were washed with brine, dried over anhydrous sodium sulfate. Filtered, the solvent was distilled under reduced pressure. To the residue was added phosphorus oxychloride (60 mL), and heated to reflux and stirred for 4h. The phosphorus oxychloride was evaporated under reduced pressure, the residue was poured into ice water and adjusted pH to neutral with sodium carbonate. Filtered, the solvent was evaporated under reduced pressure, the residue was purified by Flash column chromatography (petroleum ether/ethyl acetate = 0percent'30percent) to afford compound 21.2 (1.94 g, yield: 16percent) as an organe oil. m/z: [M+H]+186Methyl 2-methyl nicotinate (1.9 g, 13.0 mmol) (represented by formula 2-a) and trichloroisocyanuric acid (3.7 g, 16.0 mmol) (represented by formula 2-b) were dissolved in dichloromethane (50 mL), and the mixture was stirred at room temperature for 18 hours. Then saturated aqueous sodium bicarbonate solution was added to the reaction solution, the mixture was extracted with dichloromethane (30 mL*2), the dichloromethane layers were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was purified by column chromatography (silica gel, petroleum ether/ethyl acetate=100percent to 75percent) to give methyl 2-(chloromethyl)nicotinate represented by formula 2-c (1.9 g, 10.3 mmol) as a pale yellow solid. LC-MS: m/z: (M+H)+=186.

Methyl 2-Methylnicotinate is an ester derivative of nicotinic acid used in the preparation of bicyclic nitrogen containing heterocycles.Methyl 2-Methylnicotinate is a pyrolysis product of cocaine.