- Synthesis method of canagliflozin
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The invention relates to a synthesis method of canagliflozin. According to the synthesis method, 4-fluorophenylboronic acid is taken as an initial raw material to be coupled with 2-methyl-5-bromo-thiophene to synthesize 2-methyl-5-(4-fluorophenyl)thiophene, the 2-methyl-5-(4-fluorophenyl)thiophene undergoes bromation and then undergoes Friedel-Crafts alkylation reaction with 4-bromotoluene to synthesize 2-(2-methyl-5-bromobenzyl)-5-(4-fluorophenyl)thiophene, and the 2-(2-methyl-5-bromobenzyl)-5-(4-fluorophenyl)thiophene undergoes condensation, etherification and methoxyl removal with 2,3,4,6-tetra-O-trimethylsilyl-D-gluconolactone to obtain the hypoglycemic drug canagliflozin. The synthesis method has the following advantages: compared with the conventional synthesis methods, the synthesisprocess takes the 4-fluorobenzeneboronic acid as an initial raw material, so that the raw material is cheap and easy to get, the process is easy to realize industrialization, the synthesis route is short and the operation is easy; in the synthesis process, bromine is not used or butyl lithium does not need to be used twice, so that the risk of the process can be reduced; in addition, the synthesis method is capable of improving the yield of canagliflozin products to 70% or more.
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- Defluorinated canagliflozin compound, and preparation method and application thereof
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The invention relates to a defluorinated canagliflozin compound as shown in a formula (I) which is described in the specification, and a preparation method thereof. Moreover, the invention also provides application of defluorinated canagliflozin as a standard reference substance. According to the invention, the quality of a canagliflozin product is effectively controlled, so safety and validity of a canagliflozin preparation in clinical usage are guaranteed.
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