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Preparation method of 8-chloro-1-methyl-2,3,4,5-tetrahydro-1h-3-benzazepine

A technology of chlorophenylacetonitrile and trimethylchlorosilane, which is applied in the preparation of amino compounds, organic compounds, carboxylic acid amides, etc., and can solve the problems of high cost and difficult to obtain in large quantities

Active Publication Date: 2016-08-31
NANJING TECH UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The raw material p-chlorophenyl acetate used in this route is not a common industrial raw material, it is not easy to obtain in large quantities, and the cost is relatively high

Method used

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  • Preparation method of 8-chloro-1-methyl-2,3,4,5-tetrahydro-1h-3-benzazepine
  • Preparation method of 8-chloro-1-methyl-2,3,4,5-tetrahydro-1h-3-benzazepine
  • Preparation method of 8-chloro-1-methyl-2,3,4,5-tetrahydro-1h-3-benzazepine

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0066] Embodiment 1, the preparation of formula I compound:

[0067] 1.5g of the compound of formula III (6.09mmol) and 1.63g of aluminum chloride (12.19mmol) were placed in a 500mL three-necked flask, heated to 150°C, melted and stirred for 8 hours, then stopped the reaction. The reaction system to prepare the compound of formula II was cooled to room temperature, and 60 mL of treated anhydrous tetrahydrofuran was added under an ice bath to dissolve part of the reactants. After stirring for five minutes, 0.21 g of sodium borohydride (5.72 mmol) was added under an ice bath, and stirred for five minutes. , heated to 60°C and stirred for 48 hours.

[0068] After the reaction is over, under ice bath conditions, slowly add ice water dropwise to quench the reaction, add 10mL of 5% dilute hydrochloric acid and stir for half an hour, add 80mL of ethyl acetate to dilute the system, oscillate and stand for stratification, separate the water phase, add saturated carbonic acid Adjust th...

Embodiment 2

[0069] Embodiment 2, the preparation of formula I compound:

[0070] 1.5g of compound of formula III (6.09mmol) and 1.46g of aluminum chloride (10.97mmol) were placed in a 500mL three-necked flask, heated to 150°C, melted and stirred for 8 hours to stop the reaction. The reaction system to prepare the compound of formula II was cooled to room temperature, and 60 mL of treated anhydrous tetrahydrofuran was added under ice bath to dissolve part of the reactants. After stirring for five minutes, 0.58 g of sodium borohydride (15.26 mmol) was added under ice bath, and stirred for five minutes. , heated to 60°C and stirred for 36 hours.

[0071] After the reaction is over, under ice bath conditions, slowly add ice water dropwise to quench the reaction, add 10mL of 5% dilute hydrochloric acid and stir for half an hour, add 80mL of ethyl acetate to dilute the system, oscillate and stand for stratification, separate the water phase, add saturated carbonic acid Adjust the pH to 9-10 wi...

Embodiment 3

[0072] Embodiment 3, the preparation of formula I compound:

[0073] Place 2.00g of compound of formula III (8.13mmol) and 1.63g of aluminum chloride (12.19mmol) in a 500mL three-necked flask, heat to 150°C, melt and stir for 8 hours, then stop the reaction. The reaction system to prepare the compound of formula II was cooled to room temperature, and 40 mL of 1,2-dichloroethane was added under ice bath to dissolve part of the reactants. After stirring for five minutes, 0.79 g of sodium borohydride (20.99 mmol) was added under ice bath, and stirred for five minutes. minutes, heated to 60°C and stirred for 20 hours.

[0074] After the reaction, under ice bath conditions, slowly add ice water dropwise to quench the reaction, add 10mL of 5% dilute hydrochloric acid and stir for half an hour, add 80mL of ethyl acetate to dilute the system, oscillate and stand for stratification, separate the water phase, add saturated carbonic acid Adjust the pH to 9-10 with sodium solution, extra...

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Abstract

The invention discloses a preparation method of 8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzoazatropylidene. The preparation method comprises the following steps: firstly, enabling a compound with a formula (III) to react with aluminium chloride to obtain a compound with a formula (II); and carrying out reduction reaction on the compound with the formula (II) under the combined action of sodium borohydride and aluminium chloride used in the step i) to obtain a compound in a formula (I). The invention also discloses a method for preparing a compound with a formula (V) or a salt thereof. The method comprises the following steps: with chlorobenzyl cyanide and 2-chloropropionic acid as raw materials, reacting under the existence of a carboxylic acid activation reagent to generate a compound in a formula (IV); and carrying out reduction reaction on the compound with the formula (IV) under the action of a reducing agent to obtain the compound with the formula (V). Compared with the prior art, the method disclosed by the invention has the advantages of low cost, convenience for operation, safety of production, high yield and the like.

Description

technical field [0001] The invention belongs to the field of organic synthesis, and specifically relates to a preparation method of 8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine and its intermediate. Background technique [0002] Serotonin is an important inhibitory neurotransmitter in the central system. Through its effect on the ventromedial nucleus and lateral area of ​​the hypothalamus, it can make patients feel full, thereby reducing food intake and achieving the goal of weight loss. Among them, the 5-HT2C receptor subtype has a close relationship with suppressing appetite. [0003] Lorcaserin is a drug that acts on the central nervous system to suppress appetite. It was developed by Alina Pharmaceuticals of the United States in 2005. Its specific target is 5-HT2C, which has a strong effect on appetite control. There was no role for -HT2A or 5-HT2B receptors, which are associated with cardiovascular disease and hallucinations, respectively. [0004] Since all ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D223/16C07C209/50C07C211/29
CPCC07C209/50C07C231/06C07D223/16C07C211/29C07C233/91
Inventor 周国春徐斌王德才
Owner NANJING TECH UNIV
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