A kind of preparation method of greencaserin key intermediate I

A green caserin, intermediate technology, applied in the preparation of organic compounds, chemical instruments and methods, preparation of amino hydroxy compounds, etc., can solve the problem of boron trifluoride ether complex with high toxicity, unsuitable for industrial applications, and environmental pollution. Large and other problems, to achieve the effect of low cost, simple operation and high yield

Active Publication Date: 2021-03-23
GUANGZHOU TROJAN PHARMATEC LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The reduction catalyst boron trifluoride etherate complex used in this route is highly toxic, flammable, and pollutes the environment, so it is not suitable for industrial applications.

Method used

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  • A kind of preparation method of greencaserin key intermediate I
  • A kind of preparation method of greencaserin key intermediate I
  • A kind of preparation method of greencaserin key intermediate I

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] A kind of embodiment of the preparation method of green caserin key intermediate I of the present invention, comprises the following steps:

[0035] (1) Preparation of 1-(4-chlorophenyl)-2-((2-hydroxypropyl)amino)ethan-1-one

[0036] Put 2,4'-dichloroacetophenone (10g, 52.9mmol), isopropanolamine (4.77g, 63.5mmol) and sodium carbonate (5.6g, 52.9mmol) into the reaction flask at room temperature, add 50ml of ethanol , stirred and heated up to 60°C for 8 hours; distilled off ethanol under reduced pressure, added water and dichloromethane to extract and separate liquids, washed the organic layer with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was spin-dried under reduced pressure to obtain a crude product. Add 30ml of petroleum ether into it, beat at 5-10°C for 30 minutes, filter and dry to obtain 11g of solid, which is 1-(4-chlorophenyl)-2-((2-hydroxypropyl)amino)ethane-1 - ketone, the yield is 92%;

[0037] After testing, 1 H NMR ...

Embodiment 2

[0042] (1) Preparation of 1-(4-chlorophenyl)-2-((2-hydroxypropyl)amino)ethan-1-one

[0043]Put 2,4'-dichloroacetophenone (10g, 52.9mmol), isopropanolamine (4.77g, 63.5mmol) and triethylamine (8g, 79.4mmol) into the reaction flask at room temperature, add 50ml of ethanol Go in, stir and heat up to 60°C for 8h. Ethanol was distilled off under reduced pressure, water and dichloromethane were added for extraction and liquid separation, the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, the filtrate was spin-dried under reduced pressure to obtain a crude product, and 30ml of petroleum ether was added into the mixture at 5-10 Slurry at ℃ for 30 minutes, filter and dry to obtain 10.1 g of solid, which is 1-(4-chlorophenyl)-2-((2-hydroxypropyl)amino)ethan-1-one, with a yield of 85% ;

[0044] (2) Preparation of Greencaserin Key Intermediate I

[0045] Dissolve 1-(4-chlorophenyl)-2-((2-hydroxypropyl)amino)ethan-1-one (10g, 43.9mmol) in ...

Embodiment 3

[0047] A kind of embodiment of the preparation method of green caserin key intermediate I of the present invention, comprises the following steps:

[0048] (1) Preparation of 1-(4-chlorophenyl)-2-((2-hydroxypropyl)amino)ethan-1-one

[0049] At room temperature, 2,4'-dichloroacetophenone (10g, 52.9mmol), isopropanolamine (11.92g, 158.7mmol) and sodium bicarbonate (8.88g, 105.8mmol) were put into the reaction flask, and 50mlN -Methylpyrrolidone, stirred and heated to 120°C for 1 hour; N-methylpyrrolidone was distilled off under reduced pressure, water and dichloromethane were added to extract and separate the liquid, the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, The filtrate was spin-dried under reduced pressure to obtain the crude product, and 30ml of petroleum ether was added into it, and it was beaten for 30 minutes at 5-10°C, filtered, and dried to obtain 10.2g of solid, which was 1-(4-chlorophenyl)-2-((2-hydroxy Propyl)am...

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Abstract

The invention discloses a preparation method of a key intermediate I of lorcaserin. The preparation method comprises the steps as follows: (1) in an organic solvent A, 2,4'-dichloroacetophenone is subjected to a condensation reaction with isopropanolamine under catalysis of alkali, and 1-(4-chlorophenyl)-2-((2-hydroxypropyl)amino)ethane-1-one is obtained; (2) the 1-(4-chlorophenyl)-2-((2-hydroxypropyl)amino)ethane-1-one obtained in the step (1) is subjected to catalytic reduction with sodium borohydride and acid in a solvent B, and the key intermediate I of lorcaserin is obtained. The preparation method can synthesize the key intermediate I of lorcaserin from cheap and easily available raw materials under mild reaction conditions, has the advantages of being simple to operate, low in costand high in yield, and is energy-saving, environmentally friendly and suitable for mass production.

Description

technical field [0001] The invention belongs to the technical field of medicine preparation, and in particular relates to a preparation method of a key intermediate I of chlorcaserin. Background technique [0002] Lorcaserin orcaserin, trade name Belviq, is a new type of weight loss drug approved by the US FDA for the first time in 13 years. Obesity can cause various diseases, such as cerebral embolism, coronary heart disease, hypertension, fatty liver, cardiopulmonary failure, endocrine and metabolic diseases, etc. On June 27, 2012, the U.S. Food and Drug Administration (FDA) officially approved the listing of the new weight-loss drug lorcaserin hydrochloride of Arena Pharmaceuticals. Its mechanism of action is to stimulate the 5-hydroxytryptamine receptors in the hypothalamus to control appetite. The activation of this receptor can help patients eat less and enhance the feeling of fullness. [0003] The key intermediate I (1-(4-chlorophenethyl)amino)propan-2-ol) of green...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C213/08C07C215/08
CPCC07C213/08C07C221/00C07C215/08C07C225/16
Inventor 郑庆泉
Owner GUANGZHOU TROJAN PHARMATEC LTD
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