主权项 |
1. A method for preparing a compound of formula I,and the method comprising:
1) preparing a solution comprising: a raw material comprising 2,2-dimethylol propionic acid and a substituted aromatic aldehyde, a catalyst comprising p-toluenesulfonic acid, and a solvent comprising methylbenzene; heating and refluxing the solution for 8 h; precipitating a product; adding a saturated sodium carbonate aqueous solution and ether to the solution; allowing a resulting mixture to stand for stratification; separating an aqueous phase from an organic phase; adjusting pH value of the aqueous phase to be neutral; filtrating, and drying the aqueous phase to yield intermediate II represented by the following formula: wherein, R represents X represents a carbon atom or nitrogen atom;R1 represents a hydrogen atom, between one and five C1-C6 alkyls, between one and five C1-C6 alkoxys, between one and five C1-C6 alkenyls, between one and five C1-C6 alkynyls, between one and five hydroxyls, one or two methylenedioxys (OCH2O), one or two ethylenedioxys (OCH2CH2O), between one and five halogen atoms, between one and five nitryls, between one and five trifluoromethyls, or between one and five trifluoromethoxys;Y represents nitrogen atom, oxygen atom, or sulfur atom; andR2 represents hydrogen atom, between one and four C1-C6 alkyls, between one and four C1-C6 alkoxys, between one and four C1-C6 alkenyls, between one and four C1-C6 alkynyls, between one and four hydroxyls, between one and four halogen atoms, between one and four nitryls, between one and four trifluoromethyls, or between one and four trifluoromethoxys; 2) dissolving the intermediate II, an alkali, and 2,4,6-trichlorobenzoyl chloride, in a first organic solvent to form 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 5 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 dilute sulfuric acid to the second organic solvent to yield a mixed solution; allowing the mixed solution to react at a temperature of between −10 and 20° C. for between 60 and 80 h; adding ethyl acetate and water to the mixed solution, allowing the mixed solution to stand for stratification; separating an aqueous phase from an organic phase; extracting the aqueous phase by ethyl acetate to produce a new organic phase; combining the two organic phases, precipitating and purifying a resulting product by silica gel column chromatography to yield the compound. |