Preparation method of 5,5-difluoro-3-substituted piperidine derivative

Abstract

The invention relates to a preparation method of a 5,5-difluoro-3-substituted piperidine derivative. The method comprises the following steps: (1) by taking a compound 2 as a starting material, reducing the compound 2 at 0-80 DEG C to generate a compound 3; (2) dehydrating the compound 3 to generate a compound 4; (3) carrying out Pd-C catalysis and H2 reduction on the compound 4 at the temperature of 0-70 DEG C to generate a compound 5; and (4) further reacting the compound 5 to generate the 5,5-difluoro-3-substituted piperidine derivative 1, and the reaction formula of the derivative 1 is as shown in the specification, wherein R1 is ester group, carboxyl, hydroxymethyl, amino, acetyl amino, trifluoro acetyl amino, benzylamine or R3 is C1-C9 alkyl, aryl or benzyl; R2 is hydrogen, C1-C9 alkyl, aryl, hydroxymethyl, benzyl or R4 is C1-C9 alkyl, aryl or benzyl, and the groups are not substituted or substituted by one or a plurality of substituents consisting of selected free alkyl, halide alkyl, hydroxy alkyl, halogen, alkoxy or hydroxy.

Description

technical field The present invention relates to a synthesis of organic compounds, more specifically to a preparation method of 5,5-difluoro-3-substituted piperidine derivatives. Background technique Due to the uniqueness of fluorine atoms, the introduction of organic molecules can bring dramatic changes to the molecular activity and its pharmacological properties, especially in the development of safe and selective drug molecules. Thereby attracting more and more pharmacists and pharmaceutical companies to join the ranks of fluorine-containing drug research and development (Klaus Müller, Christoph Faeh, Diederich, Sceience, 2007,317,1881, O'Hagan, D., Chem.Soc.Rev .,2008,37,308;Purser,S.;Moore,P.R.;Swallow,S.;Gouverneur,V,.Chem.Soc.Rev.,2008,37,320;Kirk,K.L.,Org.Process Res.Dev.,2008, 12, 305; Isanbor, C.; O'Hagan, D., J. Fluorine Chem., 2006, 127, 992; Krik, K.L, J. Fluorine Chem., 2006, 127, 992). The piperidine structure is a very important class of intermediates in t...

AI Technical Summary

Problems solved by technology

The purpose of the present invention is to overcome the disadvantages of high cost in the preparation of 5,5-difluoro-3-substituted piperidine compounds in the prior art, difficult to purify the product, and the inability to realize industrial production, etc., and provide a relatively mild reaction condition, the product The method for preparing the compound is single, high in yield, and can be easily scaled up for industrial production