Propionyl-L-carnitine synthesis technology and detection method of related substance and its content

Abstract

A process for synthesizing the propionyl-L-carnitine features the acylation reaction between L-carnitine and propionyl chloride in propionic acid as solvent under the catalysis of p-toluenesulfonic acid. The method for measuring the contents of propionyl-L-carnitine and associated substances features that the efficient liquid-phase chromatography is used to measure the content of propionyl-L-carnitine and the thin-layer chromatography is used to detect associated substances.

Description

technical field

[0001] The invention relates to a synthesis process of propionyl-L-carnitine hydrochloride. Background technique

[0002] The synthesis method announced by British Patent 2048268A is to dissolve L-carnitine in trifluoroacetic acid, add propionyl chloride dropwise, react and filter at 40-50 degrees Celsius, and use trifluoroacetic acid as a solvent, which has high cost, heavy pollution, and dangerous operation for workers. Large, but the use of other solvents has problems such as difficulty in dissolving and many by-products, so the choice of solvent is the key and difficult point restricting the synthesis process. For the synthesis process of propionyl-L-carnitine chloride (propionyl-L-carnitine chloride), there is no public report yet. Contents of the invention

[0003] The purpose of the present invention is to provide a synthesis process of propionyl-L-carnitine hydrochloride with low raw material cost, low pollution, low risk of workers' operation, eas...

Examples

Embodiment 1

[0010] The synthesis process of propionyl-L-carnitine hydrochloride of the present invention is as follows: take 16.2 grams of L-carnitine, add 3 grams of p-toluenesulfonic acid, dry propionic acid with 40 grams, stir and dissolve, add propionyl chloride 30 gram, the temperature was raised to 45 degrees centigrade after dropping, and the insulation reaction was carried out for 20 hours. After the reaction, take it out and cool to room temperature, add 410 grams of acetone, stir for 2 hours, filter, add 490 grams of diethyl ether to the filtrate, stir until a white precipitate precipitates, and put it in the refrigerator for refrigeration. Filter and dry to obtain 22.5 g of propionyl-L-carnitine hydrochloride, with a yield of 88.2%.

Embodiment 2

[0012] The synthesis process of propionyl-L-carnitine hydrochloride of the present invention is as follows: get 18 grams of L-carnitine hydrochloride, add 6 grams of p-toluenesulfonic acid, dry propionic acid with 60 grams, stir and dissolve, add dropwise 5 grams of propionyl chloride, the temperature was raised to 50 degrees Celsius after dropping, and the temperature was kept for 20 hours. After the reaction, take it out and cool to room temperature, add 390 grams of acetone, stir for 2 hours, filter, add 510 grams of diethyl ether to the filtrate, stir until a white precipitate precipitates, and put it in the refrigerator for refrigeration. Filter and dry to obtain 24.8 g of propionyl-L-carnitine hydrochloride, with a yield of 88.3%.

Embodiment 3

[0014] The synthesis technique of propionyl-L-carnitine hydrochloride of the present invention is as follows: get 16 grams of L-carnitine, add 2 grams of p-toluenesulfonic acid, with 40 grams of propionic acid, stirring and dissolving, add dropwise 30 grams of propionyl chloride After dropping, the temperature was raised to 45 degrees centigrade, and the temperature was kept for 20 hours. After the reaction, take it out and cool to room temperature, add 410 grams of acetone, stir for 2 hours, filter, add 490 grams of diethyl ether to the filtrate, stir until a white precipitate precipitates, and put it in the refrigerator for refrigeration. Filter and dry to obtain 22.1 g of propionyl-L-carnitine hydrochloride, with a yield of 88.0%.

technical field

[0001] The invention relates to a synthesis process of propionyl-L-carnitine hydrochloride. Background technique

[0002] The synthesis method announced by British Patent 2048268A is to dissolve L-carnitine in trifluoroacetic acid, add propionyl chloride dropwise, react and filter at 40-50 degrees Celsius, and use trifluoroacetic acid as a solvent, which has high cost, heavy pollution, and dangerous operation for workers. Large, but the use of other solvents has problems such as difficulty in dissolving and many by-products, so the choice of solvent is the key and difficult point restricting the synthesis process. For the synthesis process of propionyl-L-carnitine chloride (propionyl-L-carnitine chloride), there is no public report yet. Contents of the invention

[0003] The purpose of the present invention is to provide a synthesis process of propionyl-L-carnitine hydrochloride with low raw material cost, low pollution, low risk of workers' operation, eas...

Examples

Embodiment 1

[0010] The synthesis process of propionyl-L-carnitine hydrochloride of the present invention is as follows: take 16.2 grams of L-carnitine, add 3 grams of p-toluenesulfonic acid, dry propionic acid with 40 grams, stir and dissolve, add propionyl chloride 30 gram, the temperature was raised to 45 degrees centigrade after dropping, and the insulation reaction was carried out for 20 hours. After the reaction, take it out and cool to room temperature, add 410 grams of acetone, stir for 2 hours, filter, add 490 grams of diethyl ether to the filtrate, stir until a white precipitate precipitates, and put it in the refrigerator for refrigeration. Filter and dry to obtain 22.5 g of propionyl-L-carnitine hydrochloride, with a yield of 88.2%.

Embodiment 2

[0012] The synthesis process of propionyl-L-carnitine hydrochloride of the present invention is as follows: get 18 grams of L-carnitine hydrochloride, add 6 grams of p-toluenesulfonic acid, dry propionic acid with 60 grams, stir and dissolve, add dropwise 5 grams of propionyl chloride, the temperature was raised to 50 degrees Celsius after dropping, and the temperature was kept for 20 hours. After the reaction, take it out and cool to room temperature, add 390 grams of acetone, stir for 2 hours, filter, add 510 grams of diethyl ether to the filtrate, stir until a white precipitate precipitates, and put it in the refrigerator for refrigeration. Filter and dry to obtain 24.8 g of propionyl-L-carnitine hydrochloride, with a yield of 88.3%.

Embodiment 3

[0014] The synthesis technique of propionyl-L-carnitine hydrochloride of the present invention is as follows: get 16 grams of L-carnitine, add 2 grams of p-toluenesulfonic acid, with 40 grams of propionic acid, stirring and dissolving, add dropwise 30 grams of propionyl chloride After dropping, the temperature was raised to 45 degrees centigrade, and the temperature was kept for 20 hours. After the reaction, take it out and cool to room temperature, add 410 grams of acetone, stir for 2 hours, filter, add 490 grams of diethyl ether to the filtrate, stir until a white precipitate precipitates, and put it in the refrigerator for refrigeration. Filter and dry to obtain 22.1 g of propionyl-L-carnitine hydrochloride, with a yield of 88.0%.