A kind of preparation method of diphenylmethylamine hydrochloride
What is Al technical title?
Al technical title is built by PatSnap Al team. It summarizes the technical point description of the patent document.
A technology for benzophenone hydrochloride and benzophenone, applied in the field of medicine, can solve the problems of high reaction temperature, long reaction time, large amount of formamide, etc., and achieves the advantages of shortening reaction time, reducing energy consumption and improving yield. Effect
Active Publication Date: 2020-06-16
迪嘉药业集团股份有限公司
View PDF4 Cites 0 Cited by
Summary
Abstract
Description
Claims
Application Information
AI Technical Summary
This helps you quickly interpret patents by identifying the three key elements:
Problems solved by technology
Method used
Benefits of technology
Problems solved by technology
[0013] (1) The reaction temperature is high and requires a temperature above 180°C to react;
[0014] (2) The reaction time is relatively long, usually more than 8 hours, and the energy consumption is high;
[0015] (3) The conversion rate of the reaction is low, and many impurities are generated, which leads to the yield of compound II below the middle level (60%);
[0016] (4) The purity of diphenylmethylamine hydrochloride obtained through hydrolysis is not high;
In the disclosed reaction system, the molar ratio of benzophenone, formic acid and formamide is 1:1.9:18.3, and the amount of formamide is too large, resulting in a large amount of waste liquid after the reaction, which is not conducive to environmental protection requirements and cost control
Method used
the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more
Image
Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
Click on the blue label to locate the original text in one second.
Reading with bidirectional positioning of images and text.
Smart Image
Examples
Experimental program
Comparison scheme
Effect test
Embodiment 1
[0033] Example 1 Preparation of intermediate (II)
[0034] Add 100 g of benzophenone, 148 g of formamide, and 5.0 g of 200-300 mesh chromatography silica gel, raise the temperature to 185-190° C., and react for 4 hours. Sampling HPLC monitoring (area normalization method): product 96.10%, benzophenone raw material: 0.06%. Cool the reaction solution, add water, stir and disperse evenly, filter, wash and dry to obtain 112.7 g of product, yield 97.2%, HPLC purity: 97.17%.
Embodiment 2
[0035] Example 2 Preparation of intermediate (II)
[0036] Add 100 g of benzophenone, 148 g of formamide, and 10 g of 200-300 mesh chromatography silica gel, raise the temperature to 185-190° C., and react for 3 hours. Sampling HPLC monitoring (area normalization method): product 95.15%, benzophenone raw material: 0.03%. Cool the reaction solution, add water, stir and disperse evenly, filter, wash and dry to obtain 114.0 g of product, yield 98.4%, HPLC purity: 96.94%.
Embodiment 3
[0037] Example 3 Preparation of intermediate (II)
[0038] Add 100 g of benzophenone, 148 g of formamide, and 20 g of 200-300 mesh chromatography silica gel, raise the temperature to 180-185° C., and react for 3 hours. Sampling HPLC monitoring (area normalization method): product 96.43%, benzophenone raw material: 0.02%. Cool the reaction solution, add water, stir and disperse evenly, filter, wash and dry to obtain 113.4 g of product, yield 97.8%, HPLC purity: 97.34%.
the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more
PUM
Property
Measurement
Unit
purity
aaaaa
aaaaa
Login to view more
Abstract
The invention provides a preparation method of azelnidipine starting material ethylamine benzhydrylamine. The method comprises the step of using benzophenone and formamide as raw materials to carry out aLeuckart reaction. The catalyst of silicon dioxide is added into a reaction system, and thus the reaction time is drastically reduced, wherein the time is decreased to 3-4 h from 8 h, and therefore energy consumption is significantly reduced; the rough product yield of a compound II is dramatically increased and is up to 96-98%. The purity of HPLC is not lower than 96.5%, so that it is ensured that after the ethylamine benzhydrylamine obtained by hydrochloric acid hydrolysis is purified once, the yield can reach 80%, the purity is not lower than 99.9%, and the ethylamine benzhydrylamine is quite suitable for industrial production.
Description
technical field [0001] The invention relates to a method for preparing diphenylmethylamine hydrochloride, a key starting material of azedipine, by using an improved Leuckart reaction, and belongs to the technical field of medicine. Background technique [0002] Diphenylmethylamine hydrochloride is the starting material for the preparation of azedipine, which is stable to high temperature, high humidity and light, while the free diphenylmethylamine has poor stability and cannot be stored for a long time. There are three main synthetic routes of existing reports of diphenylmethylamine hydrochloride (or free base): [0003] (1) Oxime reduction method [0004] [0005] This route takes benzophenone as starting material, and it reacts with hydroxylamine to form oxime, and then obtains benzhydrylamine through reduction. The oxime reduction methods reported in the literature include reducing reagent reduction and high-pressure hydrogenation reduction, and the reducing reagents...
Claims
the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more
Application Information
Patent Timeline
Application Date:The date an application was filed.
Publication Date:The date a patent or application was officially published.
First Publication Date:The earliest publication date of a patent with the same application number.
Issue Date:Publication date of the patent grant document.
PCT Entry Date:The Entry date of PCT National Phase.
Estimated Expiry Date:The statutory expiry date of a patent right according to the Patent Law, and it is the longest term of protection that the patent right can achieve without the termination of the patent right due to other reasons(Term extension factor has been taken into account ).
Invalid Date:Actual expiry date is based on effective date or publication date of legal transaction data of invalid patent.
Login to view more