![[1-(2-amino-2-oxoethyl)cyclohexyl]acetic acid](/Databaselist/images/loading.webp)
64744-50-9Relevant academic research and scientific papers
Synthesis of N-(2,3,4,5,6-pentafluorobenzyloxy)-γ-lactams by rhodium-catalyzed cyclization of diazo amides
Budny, Marcin,Nowak, Magdalena,Wojtczak, Andrzej,Wolan, Andrzej
, p. 6361 - 6365 (2014)
Rhodium-catalyzed cyclization of N-(2,3,4,5,6-pentafluoro-benzyloxy) diazo amides leading to the corresponding γ-lactams is described. The cyclization is based on the intramolecular catalytic insertion into the C-H bond. Fourteen lactams were obtained with up to 91 % yield and 88 % ee. Gabapentin hydrochloride, a GABA analog, was also synthesized by this method, which shows that deprotection of the 2,3,4,5,6-pentafluorobenzyloxy group is possible. The rhodium-catalyzed cyclization of diazo amides, derived from O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine, is reported. The reaction leads to a variety of lactams in up to 91 % yield and 88 % ee. The developed method was applied in the synthesis of gabapentin hydrochloride, an important GABA analog.
Mechanistic investigation on 2-aza-spiro[4,5]decan-3-one formation from 1-(aminomethyl)cyclohexylacetic acid (gabapentin)
Zambon, Elena,Giovanetti, Roberto,Cotarca, Livius,Pasquato, Lucia
, p. 6739 - 6743 (2008)
The intramolecular cyclization of the amino acid gabapentin has been studied in the pH range 2.24-11.15 at 80 °C in buffered solutions and constant ionic strength, and monitoring the progress of the process by fluorimetric method and proton NMR spectrosco
Rapid and Mild Lactamization Using Highly Electrophilic Triphosgene in a Microflow Reactor
Fuse, Shinichiro,Komuro, Keiji,Otake, Yuma,Masui, Hisashi,Nakamura, Hiroyuki
supporting information, p. 7525 - 7532 (2021/03/17)
Lactams are cyclic amides that are indispensable as drugs and as drug candidates. Conventional lactamization includes acid-mediated and coupling-agent-mediated approaches that suffer from narrow substrate scope, much waste, and/or high cost. Inexpensive, less-wasteful approaches mediated by highly electrophilic reagents are attractive, but there is an imminent risk of side reactions. Herein, a methods using highly electrophilic triphosgene in a microflow reactor that accomplishes rapid (0.5–10 s), mild, inexpensive, and less-wasteful lactamization are described. Methods A and B, which use N-methylmorpholine and N-methylimidazole, respectively, were developed. Various lactams and a cyclic peptide containing acid- and/or heat-labile functional groups were synthesized in good to high yields without the need for tedious purification. Undesired reactions were successfully suppressed, and the risk of handling triphosgene was minimized by the use of microflow technology.
NOVEL PHARMACEUTICAL COMPOSITIONS
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Paragraph 00133-00135, (2017/07/08)
The present invention relates to a pharmaceutical composition comprising a plurality of layered double hydroxide nanoparticles and one or more pharmaceutically acceptable excipients, wherein the at least one aqueously unstable anionic drug compound is intercalated between the layers. The present invention also relates to a process for the preparation of such pharmaceutical compositions, the corresponding layered double hydroxides, as well as methods for their use in stablising unstable anionic drug compounds.
A Simple and Expedient Procedure for the Preparation of Gabapentin Lactam (2-Aza-spiro[4,5]decan-3-one)
Katuri, Jashuva V. P.,Ekkundi, Vadiraj S.,Nagarajan, Kuppuswamy
, p. 1828 - 1832 (2016/10/31)
A novel process has been described on 100 g scale for the preparation of gabapentin lactam which is a penultimate intermediate for the preparation of gabapentin, comprising a Hofmann reaction of 1,1-cyclohexanediacetic acid monoamide using chlorinating agents such as trichloroisocyanuric acid, sodium dichloroisocyanurate, 1,3-dichloro-5,5-dimethylhydantoin, and N-chlorosuccinimide, which have not been employed so far for making this molecule. Reactions done in aqueous alkali on the 1,1-cyclohexanediacetic acid monoamide led to a solution of gabapentin sodium salt which on heating led to the formation of the gabapentin lactam in good yield.
Chemoenzymatic synthesis of gabapentin by combining nitrilase-mediated hydrolysis with hydrogenation over Raney-nickel
Xue, Ya-Ping,Wang, Ying-Peng,Xu, Zhe,Liu, Zhi-Qiang,Shu, Xin-Rui,Jia, Dong-Xu,Zheng, Yu-Guo,Shen, Yin-Chu
, p. 121 - 125 (2015/04/14)
An efficient chemoenzymatic process is devised for synthesizing high-purity gabapentin. 1-Cyanocyclohexaneacetic acid was first produced in 0.94 M from 1.0 M 1-cyanocycloalkaneacetonitrile by a greatly improved nitrilase from Acidovorax facilis ZJB09122, resulting in a commercially attractive bioprocess with an outstanding space-time yield of 461 g/L/day. The resulting aqueous 1-cyanocycloalkaneacetic acid was then directly converted to 2-azaspiro [4.5] decan-3-one without further purification in subsequent hydrogenation by Raney-nickel, followed by simple chemical steps to afford gabapentin in high purity and 77.3% overall yield from 1-cyanocyclohexylacetonitrile. The simplicity of the process makes this new pathway suitable for large-scale preparation.
A PROCESS FOR THE PREPARATION OF GABAPENTIN
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Page/Page column 24-25, (2014/01/09)
The present invention provides an improved process for the preparation of a compound of formula (I),
Effect of catalytic alkali metal bromide on Hofmann-type rearrangement of imides
Moriyama, Katsuhiko,Ishida, Kazuma,Togo, Hideo
supporting information; experimental part, p. 8574 - 8576 (2012/09/07)
The Hofmann-type rearrangement of aromatic and aliphatic imides using KBr as the catalyst proceeded to provide aromatic and aliphatic amino acid derivatives. We have also developed a new synthetic route to gabapentin with this method.
CRYSTALLINE FORMS OF GABAPENTIN AND PROCESS THEREOF
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Page/Page column 15-16, (2010/04/06)
The present invention relates to crystalline forms of gabapentin and processes for preparing the same. The present invention particularly relates to crystalline forms of gabapentin form II and Form IIB. The invention also relates to gabapentin form IA and form IB. The gabapentin forms IA and IB are hydrated forma that contain about 20% of water by weight which corresponds to hemipentahydrate. The present invention also relates to the process for preparing these crystalline forms of gabapentin.
A Process Suitable for Industrial Scale Production of Gabapentin
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Page/Page column 3-4, (2008/06/13)
This invention relates to an improved process for the preparation of substantially pure, stable anhydrous gabapentin. Thus, cyclohexane 1,1-diacetic acid monoamide is first treated with NaOH/NaClO to form 3,3-pentamethylenebutyrolactam, which is treated with aqueous HCl solution under reflux to provide gabapentin HCl salt, which is then neutralized with NaOH followed by a dehydration step to provide substantially pure, storage-stable, pharmaceutical grade gabapentin.
