19982-07-1Relevant articles and documents
Amidation of 1-bromo-3,5-dimethyladamantane catalyzed with manganese compounds and complexes
Khusnutdinov,Shchadneva,Khisamova
, p. 1771 - 1772 (2015)
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Process Safety Evaluation to Identify the Inherent Hazards of a Highly Exothermic Ritter Reaction Using Adiabatic and Isothermal Calorimeters
Veedhi, Srinivasarao,Babu, Subramani Ramesh
, p. 1597 - 1602 (2013)
This paper describes the process safety studies that were carried out prior to the scale-up for the initial process containing the reaction of 1,3-dimethyladamantane with sulfuric acid and acetonitrile. The reaction temperature is set at 13 C followed by heating to 23 C for progress of the reaction. Thermal screening studies showed the exotherm onset to occur at 30 C, which is very close to the desired final process temperature, with high rate of temperature rise and pressure rise. Also understood was the better option for selecting the sequence of reagent addition, i.e., either acetonitrile or sulfuric acid. These thermal hazard evaluation results helped to redesign the process temperature at 38 ± 2 C, which was evaluated for safety aspects to prevent the untoward situation using an adiabatic calorimeter and an isothermal reaction calorimeter.
Two Step Cost-Saving Process for Industrial Scale Production of 1-Amino-3,5-dimethyladamantane Hydrochloride (An Anti-Alzheimer's Drug)
Le, Viet Duc,Ngo, Sy Thinh,Nguyen, Thi Hong Tham,Nguyen, Thi Hong Thanh,Phan, Dinh Chau,Vu, Binh Duong
, p. 251 - 255 (2022/01/21)
This work presents a predominant cost-saving process for the industrial scale synthesis of memantine hydrochloride (1) from 1,3-dimethyladamantane (2) by a two-step method in which both steps were carried out in one-pot. The conversion of 2 to N-(3,5dimethyladamantane-1-yl)acetylamide (3) was synthesized first in mixture of sulfuric acid 96-98% and nitric acid 64-65% at 25 oC for 2.5 h and then in acetonitrile at 40 oC for 3.5 h as a key step. The yield of this process reached to 98%. Next, the deacetylation of 3 with potasium hydroxide in mixture of water-ethylene glycol at 140 oC for 15 h to get memantine base which was then converted into memantine hydrochloride (1) by aq. HCl 14% (yield of 93%). Overall yield of this synthetic route was 91.65%. The advantages of this process is saving time, solvents, reagents and giving a higher yield as compared to reported procedures.
Green preparation method of memantine
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Paragraph 0047; 0049; 0051; 0053; 0055, (2021/09/15)
The method comprises the following steps: (1) mixing 1 - chlorine -3 and 5 - dimethyl adamantane with acetamide to obtain 1 -acetylamino -3 and 5 -dimethyladamantane. (2) The 1 -acetylamino -3, 5 -dimethyladamantane was deacetylated in a hot-water system to obtain a memantine. The preparation method provided by the invention is simple to operate. The method is safe, environment-friendly, high in yield and purity, cost-saving, low in production cost and beneficial to industrial production.
Preparation method of medicine for treating neurological function diseases
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Paragraph 0022-0024; 0026-0028; 0030-0032; 0034-0036, (2020/11/23)
The invention discloses a preparation method of a medicine for treating neurological function diseases, which comprises the following steps: 1) adding 1-bromo-3,5-dimethyl adamantane, acetonitrile, acatalyst 1 and a catalyst 2 into a reaction kettle, stirring to react, adding a certain amount of water into the reaction solution, cooling to precipitate a solid, adding the solid into a certain proportion of an alcohol water solution, and carrying out hot melting and cold precipitation to obtain 1-acetamido-1,3-dimethyl adamantane; and (2) carrying out high-temperature reaction on 1-acetamido-1,3-dimethyl adamantane and sodium hydroxide in ethylene glycol, adding a certain amount of purified water, extracting by adopting dichloromethane, concentrating under reduced pressure, adding an ethylacetate hydrochloride solution into the concentrated solution, cooling to allow crystal growing, carrying out suction filtration, and drying to obtain memantine hydrochloride. According to the method,the catalyst 1 and the catalyst 2 are used as reaction catalysts, so that the operation risk caused by the use of concentrated sulfuric acid is avoided, the reaction time is shortened, and the side reaction is reduced. The post-treatment is simple, the reaction yield is high, and the product purity is good.