Preparation method of 2-methyl-5-(1-methylpyrrolidine-2-yl) pyridine

Abstract

The invention relates to a preparation method of 2-methyl-5-(1-methylpyrrolidine-2-yl) pyridine, the 2-methyl-5-(1-methylpyrrolidine-2-yl) pyridine is prepared by taking 6-methyl nicotinate as a raw material, and the preparation route is as follows: R1 is alkyl with 1-4 carbon atoms, such as methyl, ethyl, propyl or butyl; r2 is hydrogen, methyl or ethyl; m is Na, K or Li. According to the preparation method, the raw materials are easy to obtain, the purity and the yield can meet the industrial production requirements, compared with nicotine racemate, the obtained product 2-methyl-5-(1-methylpyrrolidine-2-yl) pyridine has better sensory test data, when the electronic cigarette atomized liquid is prepared, the effect of 3 mg / ml of natural nicotine can be achieved with the dosage of 1.5 mg / mL, and sensory experience is good.

Description

technical field

[0001] The invention relates to the field of organic synthesis, in particular to a preparation method of 2-methyl-5-(1-methylpyrrolidin-2-yl)pyridine. Background technique:

[0002] In recent years, with the advancement of science and technology, domestic tobacco companies have continuously promoted the development of new tobacco products. Among them, electronic cigarettes, as an extremely important form of new tobacco, have experienced explosive growth, while nicotine (commonly known as nicotine) , as the core functional ingredient of the entire e-cigarette industry, the demand is increasing day by day.

[0003] At present, most of the nicotine sold on the market is mainly extracted from tobacco, but the output is seriously affected by external factors such as climate, tobacco raw material output, growth cycle, etc., and the nicotine extracted from tobacco will inevitably contain masmin, The components such as neonicotinoid, dehydroneonicotinoid, and nitros...

Examples

Embodiment 1

[0031] (1) Take 400g of methyl 6-methylnicotinate, 300g of vinylpyrrolidone, and 255g of sodium tert-butoxide. Under the protection of nitrogen, add 2L of toluene and mix well, then heat to 110°C and reflux. The product is precipitated in solid form and passed through LC -MS monitors the completion of the reaction. After 8 hours of reaction, the toluene solvent is filtered, washed three times with 300g of petroleum ether, and dried at 30°C for 2 hours to obtain 1-methyl-3-(6-methyl-nicotinoyl)-2- Vinylpyrrolidone salt 583g.

[0032] (2) 583g of 1-methyl-3-(6-methyl-nicotinoyl)-2-vinylpyrrolidone salt was obtained in step (1), added 1.25kg of 36% concentrated hydrochloric acid, heated to 88°C, and passed LC-MS Monitor the completion of the reaction and react for 44h.

[0033] (3) Cool down to -20°C, add 40% potassium hydroxide aqueous solution to adjust the pH to 11, add 570g of sodium dithionite solid, stir and react at 75°C, monitor the completion of the reaction by LC-MS, a...

Embodiment 2

[0041] Other conditions and operations were the same as in Example 1, except that the reducing agent in step 3 was 343g lithium triethylborohydride, and step 3 obtained 263g of 2-methyl-5-(pyrrolidin-2-yl)pyridine. Finally, 235 g of pure 2-methyl-5-(1-methylpyrrolidin-2-yl)pyridine was obtained, with a GC purity of 99.2%. Based on 6-methylnicotinic acid methyl ester, the total yield was 50.00%.

Embodiment 3

[0043] Other conditions and operation are identical with embodiment 1, and difference is that reducing agent is 443g sodium dithionite and 77g lithium triethylborohydride in step 3, and step 3 obtains 2-methyl-5-(pyrrolidin-2-yl)pyridine 307g. Finally, 276 g of pure 2-methyl-5-(1-methylpyrrolidin-2-yl)pyridine was obtained, with a GC purity of 99.3%. Based on 6-methylnicotinic acid methyl ester, the total yield was 58.78%.

technical field

[0001] The invention relates to the field of organic synthesis, in particular to a preparation method of 2-methyl-5-(1-methylpyrrolidin-2-yl)pyridine. Background technique:

[0002] In recent years, with the advancement of science and technology, domestic tobacco companies have continuously promoted the development of new tobacco products. Among them, electronic cigarettes, as an extremely important form of new tobacco, have experienced explosive growth, while nicotine (commonly known as nicotine) , as the core functional ingredient of the entire e-cigarette industry, the demand is increasing day by day.

[0003] At present, most of the nicotine sold on the market is mainly extracted from tobacco, but the output is seriously affected by external factors such as climate, tobacco raw material output, growth cycle, etc., and the nicotine extracted from tobacco will inevitably contain masmin, The components such as neonicotinoid, dehydroneonicotinoid, and nitros...

Examples

Embodiment 1

[0031] (1) Take 400g of methyl 6-methylnicotinate, 300g of vinylpyrrolidone, and 255g of sodium tert-butoxide. Under the protection of nitrogen, add 2L of toluene and mix well, then heat to 110°C and reflux. The product is precipitated in solid form and passed through LC -MS monitors the completion of the reaction. After 8 hours of reaction, the toluene solvent is filtered, washed three times with 300g of petroleum ether, and dried at 30°C for 2 hours to obtain 1-methyl-3-(6-methyl-nicotinoyl)-2- Vinylpyrrolidone salt 583g.

[0032] (2) 583g of 1-methyl-3-(6-methyl-nicotinoyl)-2-vinylpyrrolidone salt was obtained in step (1), added 1.25kg of 36% concentrated hydrochloric acid, heated to 88°C, and passed LC-MS Monitor the completion of the reaction and react for 44h.

[0033] (3) Cool down to -20°C, add 40% potassium hydroxide aqueous solution to adjust the pH to 11, add 570g of sodium dithionite solid, stir and react at 75°C, monitor the completion of the reaction by LC-MS, a...

Embodiment 2

[0041] Other conditions and operations were the same as in Example 1, except that the reducing agent in step 3 was 343g lithium triethylborohydride, and step 3 obtained 263g of 2-methyl-5-(pyrrolidin-2-yl)pyridine. Finally, 235 g of pure 2-methyl-5-(1-methylpyrrolidin-2-yl)pyridine was obtained, with a GC purity of 99.2%. Based on 6-methylnicotinic acid methyl ester, the total yield was 50.00%.

Embodiment 3

[0043] Other conditions and operation are identical with embodiment 1, and difference is that reducing agent is 443g sodium dithionite and 77g lithium triethylborohydride in step 3, and step 3 obtains 2-methyl-5-(pyrrolidin-2-yl)pyridine 307g. Finally, 276 g of pure 2-methyl-5-(1-methylpyrrolidin-2-yl)pyridine was obtained, with a GC purity of 99.3%. Based on 6-methylnicotinic acid methyl ester, the total yield was 58.78%.

Images