Preparation method of 6-Chloromethylmorphanthridine

A technology of chloromethylmorphidine and phenylmethyl, which is applied in the field of preparation of 6-chloromethylmorphidine, which can solve the problems of large amount of waste water, instability, and serious environmental pollution.

Active Publication Date: 2017-10-24
BEIJING JINCHENG TAIER PHARMA CO LTD
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Whether it is phosphoric acid or general Lewis acids, they are extremely unstable in water, easy to decompose, use a large amount, cannot b

Method used

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  • Preparation method of 6-Chloromethylmorphanthridine
  • Preparation method of 6-Chloromethylmorphanthridine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] 26.0g (0.10mol) of N-[2-(phenylmethyl)phenyl]-2-chloroacetamide and 200ml of toluene were added to a 500ml four-neck flask, 2.0g (0.02mol) of concentrated sulfuric acid was added, stirred, and 0.62 g (0.001mol) of ytterbium trifluoromethanesulfonate and 1ml of DMSO, heated up to 100°C, and kept at this temperature for 2 hours. During the reaction, the water was removed. At the end of the heat preservation, about 75ml of toluene was distilled out, the temperature was lowered to 10°C, heat preservation was carried out for 1 hour, suction filtered, and dried at 50°C for 8 hours to obtain 23g of 6-chloromethylmorpholidine with a purity of 99.3% and a yield of 95.1%.

[0032] Mix the suction-filtered mother liquor and the distilled toluene, then add 26.0g of N-[2-(phenylmethyl)phenyl]-2-chloroacetamide, operate according to the above method, apply the mother liquor once to get 6-chloro 21.9 g of methylmorpholidine, with a purity of 98.7%, and a yield of 90.8%.

[0033] The ...

Embodiment 2

[0035] 26.0g (0.10mol) of N-[2-(phenylmethyl)phenyl]-2-chloroacetamide and 180ml of toluene were added to a 500ml four-neck flask, 1.0g (0.01mol) of concentrated sulfuric acid was added, stirred, and 2.93 g (0.005mol) lanthanum trifluoromethanesulfonate and 1ml DMSO, heat up to 90°C, keep warm for 2.5 hours, remove water during the reaction. At the end of the heat preservation, about 75ml of toluene was distilled out, then the temperature was lowered to 5°C, heat preservation was carried out for 2 hours, suction filtered, and dried at 40°C for 10 hours to obtain 23.1g of 6-chloromethylmorpholidine with a purity of 99.1% and a yield of 95.8%.

[0036] Mix the suction-filtered mother liquor and the distilled toluene, then add 26.0g of N-[2-(phenylmethyl)phenyl]-2-chloroacetamide, operate according to the above method, apply the mother liquor once to get 6-chloro 22 g of methyl morpholidine, with a purity of 98.9% and a yield of 91%.

Embodiment 3

[0038] Add 26.0g (0.10mol) of N-[2-(phenylmethyl)phenyl]-2-chloroacetamide and 190ml of toluene into a 500ml four-necked flask, add 3.0g (0.03mol) of concentrated sulfuric acid, stir, and add 0.98 g (0.002mol) scandium trifluoromethanesulfonate and 1ml DMSO, heat up to 95°C, keep warm for 3 hours, remove water during the reaction. At the end of the heat preservation, about 75ml of toluene was distilled out, the temperature was lowered to 2°C, heat preservation was carried out for 1 hour, suction filtered, and dried at 45°C for 9 hours to obtain 23g of 6-chloromethylmorphoprenidine with a purity of 98.7% and a yield of 95.3%.

[0039] Mix the suction-filtered mother liquor and the distilled toluene, then add 26.0g of N-[2-(phenylmethyl)phenyl]-2-chloroacetamide, operate according to the above method, apply the mother liquor once to get 6-chloro 21.8 g of methylmorpholidine, with a purity of 98.5%, and a yield of 90.5%.

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Abstract

The invention belongs to the technical field of medicinal chemistry and particularly relates to a preparation method of 6-Chloromethylmorphanthridine. The preparation method comprises the steps that under the action of concentrated sulfuric acid, N-[2-(phenyl methyl)phenyl]-2-chloroacetamide is taken as the raw material, a complex compound of a trifluoromethanesulfonic acid rare earth compound and dimethyl sulfoxide is taken as the catalyst, and dehydration cyclization is performed to prepare the 6-Chloromethylmorphanthridine. According to the preparation method of the 6-Chloromethylmorphanthridine, the complex compound of the trifluoromethanesulfonic acid rare earth compound and the dimethyl sulfoxide is taken as the catalyst, a better effect is realized, the pollution is small, the preparation method is environment-friendly, and recyclable production is realized.

Description

technical field [0001] The invention belongs to the technical field of medicinal chemistry, and in particular relates to a preparation method of 6-chloromethylmorphophenadine. Background technique [0002] 6-Chloromethylmorphinidine is an important intermediate in the synthesis of antidepressant mianserin hydrochloride and histamine H1 receptor antagonist epinastine hydrochloride. The effect of mianserin hydrochloride is similar to that of imipramine, it has anti-anxiety effect and rarely causes hypotension. It is especially suitable for the elderly and depressed patients with heart disease. It can also be used to treat primary anxiety or accompanied by depression. anxiety disorder. Epinastine hydrochloride has inhibitory effects on histamine, leukotriene C4, platelet activating factor (PAF), and serotonin, and can inhibit the release of histamine and slow-reacting substance A (SRS-A) chemical mediators. Epinastine is difficult to pass through the blood-brain barrier, has ...

Claims

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Application Information

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IPC IPC(8): C07D223/20B01J31/22
CPCB01J31/226B01J2531/37C07D223/20
Inventor 许蕾孟宾孙滨马庆双王晓光南红燕张彤
Owner BEIJING JINCHENG TAIER PHARMA CO LTD
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