Method for synthesizing 1-methyl-3-nitro-4-phenyl-2, 6-dipiperidone

Abstract

The invention discloses a method for synthesizing 1-methyl-3-nitro-4-phenyl-2, 6-dipiperidone. The method comprises adding N-methylnitroacetamide, cinnamaldehyde and additives into an organic solvent, carrying out a reaction process at 10-30 DEG C for 24-72h, then distilling to remove the organic solvent, adding dichloromethane and pyridinium chlorochromate into the reaction system, and carrying out a reaction process for 16h to obtain 1-methyl-3-nitro-4-phenyl-2, 6-dipiperidone. The method has the advantages of mild reaction conditions, simple operation and easy availability of raw materials. The 1-methyl-3-nitro-4-phenyl-2, 6-dipiperidone has good diastereoselectivity. The method has a good potential application value in preparation of piperidine drugs or piperidine intermediates.

Description

Technical field [0001] The invention belongs to the field of organic and pharmaceutical intermediate synthesis, and specifically relates to a method for synthesizing 1-methyl-3-nitro-4-phenyl-2,6-dipiperidone. Background technique [0002] Piperidine is an important molecular structure. Many drugs and natural products contain piperidine units. At present, although there have been many studies on the synthesis of piperidine structures with 3-position and 4-position substituents, they often require More synthetic steps, for example: the synthesis of many piperidine compounds is achieved by hydrogenation of pyridine (Org. Synth. 1964, 44, 86). The method of pyridine hydrogenation to synthesize piperidine is conducive to industrial scale-up, but the difficulty lies in the high cost of polysubstituted pyridine raw materials and requires more synthesis steps; Dieckman ester condensation ring closure is another common method for synthesizing polysubstituted piperidine rings ( WO2009010...

AI Technical Summary

Problems solved by technology

The above two methods have the following disadvantages: First, the synthesis method is cumbersome to operate and easily generates by-products. For example, in the first method, when the chiral addition intermediate is closed with formaldehyde and amine compounds, not only the nitro α The - position can react, and the α-position of the malonate structure of the substrate can also react, and it is easy to form a bicyclic by-product; the second is that the cost of raw materials is relatively high, such as nitroalkene, β-nitroethylamine and other raw materials, which lack commercialization The source, the cost required for synthesis is relatively high, and a catalyst is required for catalytic ring closure in the reaction; the third is that the diastereoisomer ratio of the products obtained by the above two methods, that is, the dr value, is generally between 2:1 and 25:1 , not very ideal, there is still a lot of room for improvement, too low dr value is not good for the chiral resolution of the compound

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