Method for synthesis of haloperidol drug intermediate 4-chlorobutyronitrile

The technology of a kind of haloperidol and synthetic method is applied in the synthetic field of haloperidol drug intermediate 4-chlorobutyronitrile, which can solve the problems of weak sedative effect, reduce intermediate links, reduce reaction temperature and reaction time, The effect of increasing the reaction yield

Inactive Publication Date: 2016-04-20
CHENGDU QIANYE LONGHUA PETROLEUM ENG TECH CONSULTING
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The antiemetic effect is also stro

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  • Method for synthesis of haloperidol drug intermediate 4-chlorobutyronitrile

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Example Embodiment

[0011] Example 1:

[0012] Add 1.6 mol of 1-chloro-4,4-dihydroxybutylamine (2) in the reaction vessel with a mass fraction of 60% 2-nitrophenol solution (3) 2.1 mol, 1.5 mol of alumina, and a mass fraction of 30% 300ml of cyclohexane, control the stirring speed at 130rpm, increase the temperature of the solution to 90℃, keep refluxing for 2h, reduce the temperature of the solution to 70℃, continue the reaction for 90min, lower the temperature of the solution to 6℃, stand for 70min, separate the solution, take it out The oil layer is extracted with 50% toluene for 5 times, washed with ammonium chloride solution, washed with 70% acetonitrile, washed with 65% triethylamine, dehydrated with anhydrous potassium carbonate, and washed with 90% Recrystallization from nitromethane yielded 136.45 g of 4-chlorobutyronitrile crystals, with a yield of 82%.

Example Embodiment

[0013] Example 2:

[0014] Add 1.6 mol of 1-chloro-4,4-dihydroxybutylamine (2) and a mass fraction of 62% 2-nitrophenol solution (3) 2.3 mol, 1.5 mol of alumina, and a mass fraction of 32% in the reaction vessel 300ml cyclohexane, control the stirring speed at 150rpm, increase the temperature of the solution to 92℃, keep refluxing for 3h, reduce the temperature of the solution to 72℃, continue the reaction for 95min, lower the temperature of the solution to 7℃, stand for 80min, separate the solution, take it out The oil layer is extracted with 52% toluene for 6 times, washed with ammonium chloride solution, washed with 72% propionitrile, washed with 67% triethylamine, and dehydrated with solid sodium hydroxide, at 93% Recrystallized from nitromethane, 141.44 g of 4-chlorobutyronitrile crystals were obtained, with a yield of 85%.

Example Embodiment

[0015] Example 3:

[0016] Add 1.6 mol of 1-chloro-4,4-dihydroxybutylamine (2) in the reaction vessel with a mass fraction of 65% 2-nitrophenol solution (3) 2.6 mol, 1.5 mol of alumina, and a mass fraction of 35% 300ml of cyclohexane, control the stirring speed at 170rpm, increase the temperature of the solution to 97℃, keep refluxing for 4h, reduce the temperature of the solution to 77℃, continue the reaction for 110min, lower the temperature of the solution to ℃, stand for 90min, the solution layered, take out The oil layer is extracted with 55% toluene for 7 times, washed with ammonium chloride solution, washed with 75% acetonitrile, washed with 68% triethylamine, dehydrated with anhydrous potassium carbonate, and washed with 98% Recrystallization from nitromethane yielded 153.09 g of 4-chlorobutyronitrile crystals, with a yield of 92%.

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Abstract

A method for synthesis of the haloperidol drug intermediate 4-chlorobutyronitrile comprises the steps of adding 1.6 mol of 1-chloro-4,4-dyhydroxy butyl amine, 2.1-2.6 mol of 2-nitrophenol solution, 1.5 mol of aluminum oxide and 300 ml of cyclohexane into a reaction vessel, controlling the stirring speed to be 130-170 rpm, increasing solution temperature to 90-97 DEG C, maintaining backflow for 2-4 h, reducing solution temperature to 70-77 DEG C, conducting reaction continuously for 90-110 min, reducing solution temperature to 6-9 DEG C, standing for 70-90 min, conducting solution delamination, taking an oil layer out, conducting extraction with methylbenzene for 5-7 times, conducting washing with saline solution, propionitrile and triethylamine, conducting dehydration with a dehydrating agent, and conducting recrystallization in nitromethane, so that 4-chlorobutyronitrile crystals are obtained.

Description

technical field [0001] The invention relates to a method for synthesizing haloperidol drug intermediate 4-chlorobutyronitrile. Background technique [0002] Haloperidol is mainly used for various acute and chronic schizophrenia. It is especially suitable for acute adolescent type and paranoid schizophrenia accompanied by hostility and aggressive actions. It can also be used for other types or chronic schizophrenia that are ineffective to phenothiazine treatment, anxiety neurosis, and small doses of this product. Effective, can eliminate involuntary movement, and can reduce and eliminate accompanying mental symptoms, vomiting and intractable hiccups. This product is the main representative of butyrophenone antipsychotics, its effect is similar to that of chlorpromazine, and it has strong dopamine receptor antagonistic effect. At the same dose, its dopamine receptor antagonism effect is 20 to 40 times that of chlorpromazine, so it is a powerful low-dose antipsychotic. Featu...

Claims

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Application Information

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IPC IPC(8): C07C253/00C07C253/34C07C255/10
CPCC07C253/00C07C253/34
Inventor 关艮安
Owner CHENGDU QIANYE LONGHUA PETROLEUM ENG TECH CONSULTING
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