Method for synthesizing temsirolimus

A method for synthesizing a compound of formula I,

• the method comprising:
• 1) providing a raw material comprising 2,2-dimethylol propionic acid and a substituted boric acid;
• dissolving the raw material in tetrahydrofuran to form a solution;
• allowing the solution to react at room temperature;
• adding toluene to the solution, heating, and refluxing the solution;
• and adding cyclohexane to the solution to yield intermediate II represented by the following formula:
• wherein, R represents a hydrogen atom, an alkyl group comprising between one and six carbon atoms, a cycloalkyl or substituent thereof comprising between one and six carbon atoms, an alkenyl comprising between one and six carbon atoms, an alkynyl comprising between one and six carbon atoms, a benzyl or a substituent thereof, an aromatic ring or a substituent thereof comprising between seven and twenty carbon atoms, or a heteroaromatic ring or a substituent thereof comprising between four and twenty carbon atoms;
• 2) dissolving the intermediate II in a first organic solvent;
• adding an alkali and 2,4,6-trichlorobenzoyl chloride to the first organic solvent to yield a mixture;
• allowing the mixture to react in the presence of nitrogen gas at a temperature of between −20 and 40° C. for between 4 and 8 h;
• adjusting the temperature of the mixture to −10° C.;
• adding rapamycin and an acid binding agent to the mixture, allowing the mixture to react overnight at room temperature;
• and separating a product by silica gel column chromatography to yield intermediate III represented by the following formula:
• wherein, R represents the same structure as that of the intermediate II;
• and
• 3) dissolving the intermediate III in a second organic solvent, adding a diol to the second organic solvent to yield a mixed solution;
• allowing the mixed solution to react at a temperature of between −20 and 20° C. for between 8 and 14 h;
• and precipitating and separating a resulting product by using silica gel column chromatography to yield the compound.