Synthetic method of doxylamine succinate intermediate

A technology for a cylamin intermediate and a synthesis method, which is applied in the synthesis field of the intermediate, can solve the problems of high toxicity, high cost, complicated procedures and the like, and achieves the effects of low production cost, rapid reaction and efficient purification process.

Inactive Publication Date: 2013-04-24
ZHONGSHAN BAILING BIOTECHNOLOGY CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] At present, only the doxylamine tablet of Shandong Chengchuang Pharmaceutical Technology Development Co., Ltd. has been approved as a 3.1 chemical new drug in China; the existing synthetic method of doxylamine succinate intermediate has complicated procedures, high toxicity and high cost. high

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] 1. Preparation of Grignard reagent

[0025] Take 5.52g (0.23mol) of magnesium chips and add it to a 500ml four-neck round bottom flask, add 150ml of methyl tert-butyl ether, stir, take 31.6g (0.2mol) of 2-bromopyridine and dissolve it in 200ml of methyl tert-butyl ether; First add 10ml of 2-bromopyridine in methyl tert-butyl ether solution dropwise, heat to 45°C, the reaction will start, exotherm violently, and the reaction solution will become turbid; control the temperature at 10-13°C, slowly add dropwise, and finish adding in 0.5 hours. The reaction was stirred for 1 hour.

[0026] Let it stand still for 0.5 hour, and take the metallic gray supernatant.

[0027] 2. Synthesis of 2-pyridylphenylmethylmethanol

[0028] Add 26.43g (0.22mol) of acetophenone into a 1000ml four-neck round bottom flask, dissolve in 200ml of methyl tert-butyl ether, add 4.09g (0.03mol) of anhydrous zinc chloride, stir, add Grignard reagent dropwise, and react Vigorously exothermic, tempera...

Embodiment 2

[0036] 1. Preparation of Grignard reagent

[0037] Take 1g of magnesium chips and add it to a 500ml four-necked round-bottomed flask, add 20ml of methyl tert-butyl ether, stir, take 4g of 2-bromopyridine and dissolve it in 25ml of methyl tert-butyl ether; The tert-butyl ether solution was heated to 45°C, the reaction was triggered, exothermic violently, and the reaction liquid became turbid; the temperature was controlled at 10-13°C, and slowly added dropwise, the addition was completed in 0.5 hours, and the reaction was stirred for 1 hour.

[0038] Let it stand still for 0.5 hour, and take the metallic gray supernatant.

[0039] 2. Synthesis of 2-pyridylphenylmethylmethanol

[0040] Add 5g of acetophenone into a 1000ml four-neck round bottom flask, dissolve it in 150ml of methyl tert-butyl ether, add 1.8g of BF 3 , Stir, add Grignard reagent dropwise, the reaction is violently exothermic, control the temperature at 0-3°C, add dropwise slowly, finish adding in 0.5 hours, and...

Embodiment 3

[0047] 1. Preparation of Grignard reagent

[0048] Take 10g of magnesium chips and add it to a 1000ml four-neck round bottom flask, add 500ml of methyl tert-butyl ether, stir, take 70g of 2-bromopyridine and dissolve it in 500ml of methyl tert-butyl ether; The butyl ether solution was heated to 45°C, the reaction was triggered, exothermic violently, and the reaction solution became turbid; the temperature was controlled at 10-13°C, and slowly added dropwise, the addition was completed in 0.5 hours, and the reaction was stirred for 1 hour.

[0049] Let it stand still for 0.5 hour, and take the metallic gray supernatant.

[0050] 2. Synthesis of 2-pyridylphenylmethylmethanol

[0051] Add 50g of acetophenone into a 1000ml four-neck round bottom flask, dissolve in 400ml of methyl tert-butyl ether, add 6.3g of FeCl 3 , Stir, add Grignard reagent dropwise, the reaction is violently exothermic, control the temperature at 0-3°C, add dropwise slowly, finish adding in 0.5 hours, and s...

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Abstract

The invention discloses a synthetic method of a doxylamine succinate intermediate, which is characterized by comprising the following steps of: A, 2-pyridine-phenyl methyl methanol synthesis: dissolving acetophenone into methyl tertiary butyl ether, adding a catalyst, then agitating and dropwise adding a Grignard reagent, and obtaining a target product, i.e. 2- pyridine-phenyl methyl methanol after separation and desolvation; and B, 2-pyridine-phenyl methyl methanol purification: dissolving the 2-pyridine-phenyl methyl methanol in the step A into methanol, dropwise adding acetone slowly into solution till a large amount of 2-pyridine-phenyl methyl methanol is crystallized and separated out. The invention aims to overcome the defects in the prior art and provides the synthetic method of the doxylamine succinate intermediate, which has the advantages of simple, safe and reliable process, high efficiency and low production cost.

Description

technical field [0001] The invention relates to a synthetic method of an antihistamine intermediate, in particular to a synthetic method of a doxylamine succinate intermediate, that is, a synthetic method of 2-pyridylphenylmethylcarbinol. Background technique [0002] Doxylamine succinate is an ethanol antihistamine with antihistamine, anticholinergic and sedative-hypnotic effects. It acts quickly and lasts for a short time, but the sedative effect is obvious. Doxylamine succinate is suitable for a variety of allergic skin diseases, hay fever, allergic rhinitis, etc.; it can also be used for pregnancy reactions such as nausea and vomiting in pregnant women; it produces drowsiness by inhibiting the central nervous system, and is often used as a hypnotic drug Helps reduce difficulty falling asleep. [0003] In October 1978, the FDA approved the marketing of doxylamine 25mg tablets of CHATTEM Company for the short-term treatment of insomnia. It became an over-the-counter (OTC...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D213/30
Inventor 刘骅张和平刘遗松黄文军霍延豪阮宇峰梁待亮沈惠宾周海香邱国华
Owner ZHONGSHAN BAILING BIOTECHNOLOGY CO LTD
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