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L-dopa methyl ester hydrochloride preparation method

A technology of levodopa methyl ester and hydrochloride, which is applied in the preparation of organic compounds, chemical instruments and methods, and cyanide reaction preparation, etc., which can solve the problem of strong liver toxicity, solid hygroscopicity, and can only be stored in a desiccator Medium problem, achieve the effect of short operation time, low hygroscopicity and low toxicity

Inactive Publication Date: 2009-04-15
蒋伟哲
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] Based on the above purification methods, it is known that the ether or ethanol ether mixed solvent method used in the literature needs to be placed in the refrigerator for a long time, and some even need a few days to crystallize, and cannot be crystallized at room temperature, and crystallized by these methods The solid is very hygroscopic and should only be stored in a desiccator
The purification method adopted in the above-mentioned invention patent (CN 1220674C) is more superior in product quality than the method of known literature, but the carbon tetrachloride and dichloroethane used in the production process are the first class solvents, which are harmful to the human body. Carcinogens, organic solvents suspected to be human carcinogens or environmental hazards, should be avoided in the production of raw materials, excipients and preparations; It is recommended to limit the use in production
Therefore, there are still many problems to be solved in the industrialized production of this method

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] Synthesis

[0045] Dissolve 7.5 g of levodopa in 80 ml of methanol, feed saturated hydrogen chloride gas, heat to reflux for 2.5 hours, change the reflux device to a distillation device, first remove and recover methanol by distillation under reduced pressure, raise the temperature (about 80°C) and then reduce the pressure Water was removed by distillation. Cool to below 60°C, add 80ml of methanol to the distillation residue, continue to pass in saturated hydrogen chloride gas, reheat and reflux for 2.5 hours, first remove the recovered methanol by distillation under reduced pressure, then slightly increase the temperature and then remove the water by distillation under reduced pressure, as above method A total of 4 times. After the reaction, the methanol was distilled off under reduced pressure to obtain 10.4 g of the crude product of levodopa methyl ester hydrochloride (containing a small amount of methanol and hydrogen chloride).

Embodiment 2

[0047] Synthesis

[0048] Add 100ml of methanol under cooling in an ice bath, add 10ml of thionyl chloride dropwise under stirring, then add 23g of levodopa (the temperature is less than 10°C), control the temperature at 5°C, heat to 40°C for 2.5 hours, and change the reflux device to It is a distillation device, first remove the recovered methanol by distillation under reduced pressure, then raise the temperature (about 80°C) and then remove water by distillation under reduced pressure. Cool to room temperature, add 80ml under ice bath cooling, add 10ml of thionyl chloride dropwise under stirring, heat to 40°C for 2.5 hours, first remove and recover methanol by distillation under reduced pressure, then raise the temperature slightly (about 80°C) and then distill under reduced pressure Remove moisture, carry out 2 times altogether as above method. After the reaction, the methanol was distilled off under reduced pressure to obtain an oily product which was 32.5 g of the crude ...

Embodiment 3

[0050] Purification process

[0051]Take the crude product of levodopa methyl ester hydrochloride in Example 2 for purification, add 15ml of ethanol, heat to about 60°C to dissolve, then slowly add 85ml of petroleum ether, the solution is slowly cooled, stir and mix the solution for 4 hours, filter out the product, And washed twice with 20ml of the above-mentioned petroleum ether / ethanol mixed solution, and dried in vacuum at 80°C to obtain 27.8g of a white product with a yield of 96.2%. HPLC showed that the content of levodopa methyl ester hydrochloride was greater than 99%.

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PUM

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Abstract

The invention discloses a preparing method of bendopa methyl ester hydrochlorate, which is characterized by the following: adopting bendopa and carbinol as raw material through multi-distilling dehydrating method; modifying sulfone chloride method and hydrochloride method; removing water and esterifying water; accelerating the esterifying reaction to terminal; purifying bendopa methyl ester hydrochlorate through ligarine, skellysolve B, cyclohexane, cyclopentene and heptane.

Description

technical field [0001] A method for synthesizing and purifying levodopa methyl ester hydrochloride relates to the preparation of high-purity levodopa methyl ester hydrochloride. Background technique [0002] There are few effective therapeutic drugs for the treatment of Parkinson's syndrome, and the compound preparation of levodopa (Levodopa) and its carbidopa or benserazide is still one of the most effective drugs. However, levodopa is poorly soluble and difficult to absorb. Only 1% of it enters the center and is converted into dopamine to take effect, and it has some side effects. Levodopa methyl ester (LDME) is a more important derivative of levodopa, and they use levodopa as raw material to synthesize levodopa methyl ester through a one-step reaction. Levodopa methyl ester overcomes the shortcomings of levodopa. It is easily soluble in water and easily enters the blood-brain barrier. It is easy to make various oral dosage forms and injections. It absorbs quickly, and th...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C229/36C07C227/16
Inventor 蒋伟哲
Owner 蒋伟哲
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