Chen Xin-zhi
2011
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Journal
Journal of Chemical Engineering of Chinese Universities
Abstract
tert-Butyl 4-methyl-3-oxopiperidine-1-carboxylate is an important intermediate in the synthesis of the novel protein tyrosine kinase Jak3 inhibitor—CP-690550.In this article,an efficient approach to the synthesis of this interesting compound was proposed.The proposed synthesis process consists of a series of steps: starting from the easy available reagent 4-methylpyridinium,going through the SN2 substitution with benzyl chloride to offer 1-benzyl-3-hydroxy-4-methylpyridium chloride with high yield,and then defining the suitable solvent species and its reasonable concentration for the borohydride reduction with sodium borohydride to provide N-benzyl-3-hydroxy-4-methylpiperidine,consequently,oxidation by Jones reagent under mild temperature to give N-benzyl-3-oxo-4-methylpiperdine,and at last,debenzylation with Pd/C catalyst and acylation to obtain the target product tert-butyl 4-methyl-3-oxopiperidine-1-carboxylate.The total yield can reach 80.2% by using the proposed method.Compared with the existing process,the proposed method has the advantages of easily obtained raw materials,simple in operation and suitable for industrial scale-up.