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.
Decarboxylative Ritter-Type Amination by Cooperative Iodine (I/III)─Boron Lewis Acid Catalysis
Narobe, Rok,Murugesan, Kathiravan,Schmid, Simon,K?nig, Burkhard
, p. 809 - 817 (2022/01/15)
Recent years have witnessed important progress in synthetic strategies exploiting the reactivity of carbocations via photochemical or electrochemical methods. Yet, most of the developed methods are limited in their scope to certain stabilized positions in molecules. Herein, we report a metal-free system based on the iodine (I/III) catalytic manifold, which gives access to carbenium ion intermediates also on electronically disfavored benzylic positions. The unusually high reactivity of the system stems from a complexation of iodine (III) intermediates with BF3. The synthetic utility of our decarboxylative Ritter-type amination protocol has been demonstrated by the functionalization of benzylic as well as aliphatic carboxylic acids, including late-stage modification of different pharmaceutical molecules. Notably, the amination of ketoprofen was performed on a gram scale. Detailed mechanistic investigations by kinetic analysis and control experiments suggest two mechanistic pathways.
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 synthesis method
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Paragraph 0061-0066; 0074-0074; 0088-0093, (2020/03/09)
The invention provides a memantine hydrochloride synthesis method, and belongs to the technical field of medicine synthesis. The preparation method comprises the following steps: carrying out a substitution reaction on 1-bromo-3,5-dimethyladamantane and acetamide to obtain 1-acetamido-3,5-dimethyladamantane, mixing the 1-acetamido-3,5-dimethyladamantane, an alcohol and an alkali, carrying out an alcoholysis reaction to obtain 1-amino-3,5-dimethyladamantane, and finally carrying out an acidification reaction on the 1-amino-3,5-dimethyladamantane and hydrochloric acid to obtain memantine hydrochloride. According to the method of the invention, 1-bromo-3,5-dimethyl adamantane and acetamide are used as the starting raw materials, so the sources of the raw materials are wide, the use of acetonitrile is avoided, and no pollution is caused to the human body and the environment; the use of catalysts is avoided in the whole reaction process, the reaction product is easy to separate, and the yield of the obtained memantine hydrochloride is high; and the method is mild in reaction condition and suitable for industrial production.
