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.
Memantine hydrochloride impurity compound and preparation method thereof
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Paragraph 0040-0042; 0047-0048, (2020/06/20)
The invention discloses a preparation method of a memantine hydrochloride impurity compound 1-nitro-7-hydroxy-3,5-dimethyl adamantane. According to the preparation method, 1-bromo-3,5-dimethyl adamantane is taken as a raw material and carries out a substitution reaction with acetamide in a molten state, then hydrolysis and salt forming happen in an alkaline environment, and finally the target product is prepared after hydroxylation and oxidation. The impurity compound is used as a reference substance for memantine hydrochloride quality control.