A cost effective one-pot racemization process of 3-(Carbamoylmethyl)-5- methylhexanoic acid: A Pregabalin Intermediate
نویسندگان
چکیده
This paper describes a simple, cost-effective and one pot process for racemization of undesired (S)-3-(carbamoylmethyl)-5-methylhexanoic acid, which produced during the resolution step. The unwanted S-enantiomer was converted into the symmetrical glutarimide derivative in the presence of a catalytic amount of DMAP or pyridine in refluxing toluene followed by hydrolysis with an alkali.
منابع مشابه
Pregabalin reduces the release of synaptic vesicles from cultured hippocampal neurons.
Pregabalin [S-[+]-3-isobutylGABA or (S)-3-(aminomethyl)-5-methylhexanoic acid, Lyrica] is an anticonvulsant and analgesic medication that is both structurally and pharmacologically related to gabapentin (Neurontin; Pfizer Inc., New York, NY). Previous studies have shown that pregabalin reduces the release of neurotransmitters in several in vitro preparations, although the molecular details of t...
متن کاملCost-Effective Isolation of a Process Impurity of Pregabalin
Cost-effective isolation methods were developed on preparative HPLC, flash LC, and simulated moving bed (SMB) to prepare the process impurity, 3-(aminomethyl)-5-methylhex-4-enoic acid (4-ene impurity), of pregabalin. By a thorough experimental study on the different isolation techniques available, it was concluded that SMB was the most cost-effective. Hence, it was a continuous chromatography t...
متن کاملNitrile as Activating Group in the Asymmetric Bioreduction of β-Cyanoacrylic Acids Catalyzed by Ene-Reductases
Asymmetric bioreduction of an (E)-β-cyano-2,4-dienoic acid derivative by ene-reductases allowed a shortened access to a precursor of pregabalin [(S)-3-(aminomethyl)-5-methylhexanoic acid] possessing the desired configuration in up to 94% conversion and >99% ee. Deuterium labelling studies showed that the nitrile moiety was the preferred activating/anchor group in the active site of the enzyme o...
متن کاملOne-pot, four-component synthesis of fully substituted 1,3,4-oxadiazole derivatives from N-isocyaniminotriphenylphosphorane (Ph3PNNC), a primary amine, a carboxylic acid and cinnamaldehyde
The imine intermediate generated by the addition of primary amine to the cinnamaldehyde is trapped by the N-isocyaniminotriphenylphosphorane (Ph3PNNC) and a carboxylic acid, and leads to the formation of the corresponding iminophosphorane intermediate. The 1,3,4-oxadiazole derivatives are formed via intramolecular aza-Wittig reaction of the iminophosphorane intermediate. The reactions were comp...
متن کاملHemangiosarcoma in mice administered pregabalin: analysis of genotoxicity, tumor incidence, and tumor genetics.
Pregabalin, (S)-3-(aminomethyl)-5-methylhexanoic acid, binds with high affinity to the α(2)δ subunit of voltage-gated calcium channels and exerts analgesic, anxiolytic, and antiseizure activities. Two-year carcinogenicity studies were completed in B6C3F1 and CD-1 mice and two separate studies in Wistar rats. Doses in mice were 200, 1000, and 5000 mg/kg/day, with systemic exposures (AUC(0-24 h))...
متن کامل