6740-87-0Relevant articles and documents
Process Research and Impurity Control Strategy of Esketamine
Gao, Shenghua,Gao, Xuezhi,Yang, Zhezhou,Zhang, Fuli
, p. 555 - 566 (2020/05/19)
An improved synthesis of (S)-ketamine (esketamine) has been developed, which was cost-effective, and the undesired isomer could be recovered by racemization. Critical process parameters of each step were identified as well as the process-related impurities. The formation mechanisms and control strategies of most impurities were first discussed. Moreover, the (S)-ketamine tartrate is a dihydrate, which was disclosed for the first time. The practicable racemization catalyzed by aluminum chloride was carried out in quantitative yield with 99% purity. The ICH-grade quality (S)-ketamine hydrochloride was obtained in 51.1% overall yield (14.0% without racemization) by chiral resolution with three times recycling of the mother liquors. The robust process of esketamine could be industrially scalable.
COMPOSITIONS AND METHODS FOR THE TREATMENT OF NEUROLOGICAL DISEASES
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Page/Page column 50-52, (2019/10/19)
The invention relates to the compounds or its pharmaceutical acceptable polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula I, formula II and formula III and the methods for the treatment of neurological diseases may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, lozenge, spray, intravenous, oral solution, nasal spray, oral solution, suspension, oral spray, buccal mucosal layer tablet, parenteral administration, syrup, or injection. Such compositions may be used to treatment of neurological diseases.
Expedient preparation of active pharmaceutical ingredient ketamine under sustainable continuous flow conditions
Kassin, Victor-Emmanuel H.,Gérardy, Romaric,Toupy, Thomas,Collin, DIégo,Salvadeo, Elena,Toussaint, Fran?ois,Van Hecke, Kristof,Monbaliu, Jean-Christophe M.
supporting information, p. 2952 - 2966 (2019/06/18)
A robust three-step continuous flow procedure is presented for the efficient and sustainable preparation of active pharmaceutical ingredient ketamine. The procedure relies on the main assets of continuous flow processing, starts from commercially available chemicals, utilizes low toxicity reagents and a FDA class 3 solvent under intensified conditions. The procedure features a unique hydroxylation step with molecular oxygen, a fast imination relying on triisopropyl borate and a thermolysis employing Montmorillonite K10 as a heterogeneous catalyst, all three steps being performed in ethanol. The three individual steps can be run independently or can be concatenated, thus providing a compact yet efficient setup for the production of ketamine. The scalability of the critical hydroxylation step was assessed in a commercial pilot continuous flow reactor. The process can also be adapted for the preparation of ketamine analogs. A thorough computational study on the backbone rearrangement of the cyclopentylphenylketone scaffold under thermal stress rationalizes the experimental selectivity and the various experimental observations reported herein.