102767-28-2Relevant articles and documents
Peculiar Case of Levetiracetam and Etiracetam α-Ketoglutaric Acid Cocrystals: Obtaining a Stable Conglomerate of Etiracetam
George, Fanny,Norberg, Bernadette,Robeyns, Koen,Wouters, Johan,Leyssens, Tom
, p. 5273 - 5282 (2016)
In this contribution, we demonstrate that it is possible to obtain the lactol tautomer of alpha-ketoglutaric acid (AKGA) in the solid state by cocrystallizing it with Leviteracetam, a chiral nootropic drug used to treat epilepsy. In addition, we show that a cocrystal can be isolated with the racemic equivalent of Levetiracetam, Etiracetam (Eti), in which AKGA stays in the keto-form. We also report the existence of a cocrystal conglomerate in the Etiracetam-AKGA system, which is more stable than the racemic cocrystal at room temperature. The existence of a stable conglomerate is put in relation to the enantiospecificity of the Levetiracetam cocrystals, which is likely related to the ability of the Etiracetam enantiomers to stabilize one lactol tautomer at a time in solution or to promote its formation by hydrogen bonding. By comparing the peculiarities of the system in hand to the general behavior of cocrystallizing chiral systems with and without zwitterionic coformers, we suggest that for a pseudoquaternary cocrystal (made up of two racemate compounds) to exist the pseudoternary combinations (made up of one racemate and an enantiomer of the second compound) should exist and the enantiomers of the two compounds should form a diastereomeric pair at the binary level, rather than behave enantiospecifically.
A Short Enantioselective Synthesis of (S)-Levetiracetam through Direct Palladium-Catalyzed Asymmetric N -Allylation of Methyl 4-Aminobutyrate
Albat, Dominik,Neud?rfl, J?rg-Martin,Schmalz, Hans-Günther
, p. 1089 - 1092 (2021)
An exceedingly short and enantioselective synthesis of the antiepileptic drug (S)-levetiracetam was elaborated. As the chirogenic key step, a Pd-catalyzed asymmetric N -allylation of methyl 4-aminobutyrate was achieved in the presence of only 1 mol% of a catalyst prepared in situ from [Pd(allyl)Cl] 2 and a tartaric acid-derived C 2 -symmetric diphosphine ligand.
Solid-state chiral resolution mediated by stoichiometry: Crystallizing etiracetam with ZnCl2
Shemchuk, Oleksii,Song, Lixing,Robeyns, Koen,Braga, Dario,Grepioni, Fabrizia,Leyssens, Tom
, p. 10890 - 10892 (2018)
Chiral resolution of racemic etiracetam was achieved via co-crystallization with ZnCl2. Depending on the amount of ZnCl2 either a stable racemic compound or a stable conglomerate can be obtained. Excess ZnCl2 triggers the quantitative conversion of the racemate into the conglomerate solid; this unprecedented behaviour was investigated through a racetam/ZnCl2/solvent phase diagram.
Cobalt-catalyzed asymmetric hydrogenation of enamides enabled by single-electron reduction
Friedfeld, Max R.,Zhong, Hongyu,Ruck, Rebecca T.,Shevlin, Michael,Chirik, Paul J.
, p. 888 - 893 (2018)
Identifying catalyst activation modes that exploit one-electron chemistry and overcome associated deactivation pathways will be transformative for developing first-row transition metal catalysts with performance equal or, ideally, superior to precious metals. Here we describe a zinc-activation method compatible with high-throughput reaction discovery that identified scores of cobalt-phosphine combinations for the asymmetric hydrogenation of functionalized alkenes. An optimized catalyst prepared from (R,R)-Ph-BPE (Ph-BPE, 1,2-bis[(2R,5R)-2,5-diphenylphospholano]ethane) and cobalt chloride [CoCl2·6H2O] exhibited high activity and enantioselectivity in protic media and enabled the asymmetric synthesis of the epilepsy medication levetiracetam at 200-gram scale with 0.08 mole % catalyst loading. Stoichiometric studies established that the cobalt (II) catalyst precursor (R,R)-Ph-BPECoCl2 underwent ligand displacement by methanol, and zinc promoted facile one-electron reduction to cobalt (I), which more stably bound the phosphine.
Total synthesis of levetiracetam
Narczyk, Aleksandra,Mrozowicz, Micha?,Stecko, Sebastian
, p. 2770 - 2775 (2019)
Total synthesis of levetiracetam, an active ingredient of epilepsy treatment medications, is reported. The reported method is based on a one-pot dehydration/sigmatropic rearrangement of (R,E)-hept-4-en-3-ol carbamate to the corresponding allylamine derivative, an advanced precursor of levetiracetam.
Radiosynthesis of 11C-levetiracetam: A potential marker for PET imaging of SV2A expression
Cai, Hancheng,Mangner, Thomas J.,Muzik, Otto,Wang, Ming-Wei,Chugani, Diane C.,Chugani, Harry T.
, p. 1152 - 1155 (2014)
The multistep preparation of 11C-levetiracetam (11C-LEV) was carried out by a one-pot radiosynthesis with 8.3 ± 1.6% (n = 8) radiochemical yield in 50 ± 5.0 min. Briefly, the propionaldehyde was converted to propan-1-imine in situ as labeling precursor by incubation with ammonia. Without further separation, the imine was reacted with 11C-HCN to form 11C-aminonitrile. This crude was then reacted with 4-chlorobutyryl chloride and followed by hydrolysis to yield 11C-LEV after purification by chiral high-performance liquid chromatography (HPLC). Both the radiochemical and enantiomeric purities of 11C-LEV were >98%.
Method for synthesizing medicine for treating epilepsy by using L-2-aminobutanamide hydrochloride
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Paragraph 0057-0058; 0062-0063; 0071-0072; 0076-0077, (2021/11/03)
The invention discloses a method for synthesizing a medicine for treating epilepsy by using L-2-aminobutanamide hydrochloride, and relates to the technical field of medicine synthesis, and the method comprises the following steps: under the protection of nitrogen, adding L-2-aminobutanamide hydrochloride and 4-chlorobutyrate into isopropyl alcohol, and reacting under the action of an alkaline substance and a catalyst, heating and refluxing to carry out nucleophilic substitution reaction and ring-closure reaction to prepare the levetiracetam. According to the method, the levetiracetam is synthesized by adopting a milder alkaline substance and a one-pot method, the operation is simple, the levetiracetam can be prepared without post-treatment, the levetiracetam obtained by the method is low in impurity content and high in chemical purity, the yield can reach 83.43% or above, and the purity reaches 99.6%.
Preparation method of levetiracetam
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Paragraph 0051-0055, (2021/10/20)
The invention relates to a preparation method of levetiracetam, and belongs to the technical field of medicine synthesis. In order to solve the problem that resolution is needed due to low chiral purity in the prior art, the invention provides a preparation method of levetiracetam. The method comprises the following steps: reacting 2-halogenated butyramide with 2-pyrrolidone in the presence of an acid-binding agent under the catalytic action of a catalytic amount of chiral BINOL derived phosphoric acid ligand to obtain the levetiracetam, wherein the 2-halogenated butyramide is selected from 2-chlorobutyramide or 2-bromobutyramide. The method has the characteristic of high chiral conversion rate, the effects of high product yield and high chiral purity are achieved, the yield reaches 85% or above, and the chiral purity reaches 99% or above.
