Method for preparing pitavastatin calcium epoxy impurity and nitrogen oxide impurity
A technology of pitavastatin calcium and impurities, which is applied in the field of preparation of pitavastatin calcium epoxy impurities and nitrogen oxide impurities, can solve the problems such as the preparation method of pitavastatin calcium epoxy impurities and nitrogen oxygen impurities that have not been reported in the literature, and achieve The effect of reasonable route design, high impurity purity and simple preparation method
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Embodiment 1
[0038] Add 30ml of chloroform, 4.41g of pitavastatin calcium, and 2.10g of trifluoroacetic anhydride into a 100ml single-necked flask, stir, cool down to 0°C, dissolve 2.76g of carbamide peroxide in 10ml of ethanol, add dropwise at 0°C, add dropwise After completion, keep the reaction at 0°C to 5°C for 5h. TLC detects that the reaction is complete, and 20 ml of saturated Na 2 S 2 o 3 solution, the organic layer was washed with saturated NaCl solution (20ml*3), the organic layer was dried with anhydrous magnesium sulfate, filtered, the filtrate was concentrated under reduced pressure, and separated by column chromatography [eluent: dichloromethane: methanol: glacial acetic acid = 30 :1:1], 1.65g of white solid was obtained, that is, compound 2 (epoxy impurity), the yield was 37.8%, and the liquid phase purity was 99.5%.
[0039] 1 H NMR (400MHz, d-DMSO) δ12.12(s,1H), 7.84(d,1H), 7.64(dt,1H), 7.127.48(m,6H), 4.75(d,1H), 4.49( d,1H), 4.40(s,1H), 4.33(m,1H), 3.94(s,1H), 3.90(...
Embodiment 2
[0043] Add 20ml of absolute ethanol, 4.41g of pitavastatin calcium, and 2.96g of phthalic anhydride into a 100ml single-necked flask, stir, cool down to 0°C, dissolve 3.68g of carbamide peroxide in 10ml of absolute ethanol, and add dropwise at 0°C After the dropwise addition, keep the reaction at 0°C to 5°C for 20h. TLC detects that the reaction is complete, and first adds 50ml of dichloromethane to the reaction solution, then adds 20ml of saturated Na 2 S 2 o 3 solution, the organic layer was washed with saturated NaCl solution (20ml*3), the organic layer was dried with anhydrous magnesium sulfate, filtered, the filtrate was concentrated under reduced pressure, and separated by column chromatography [eluent: dichloromethane: methanol: glacial acetic acid = 30 :1:1] to obtain 1.55 g of white solid, namely compound 2, with a yield of 35.5% and a liquid phase purity of 98.7%.
[0044] The residue was further separated by column chromatography [eluent: dichloromethane: methano...
Embodiment 3
[0046] Add 10ml dimethyl sulfoxide and 10ml N,N-dimethylformamide, 4.41g pitavastatin calcium, 1.13g benzoic anhydride to a 100ml single-necked flask, stir, cool to 0°C, dissolve 0.92g urea peroxide in Add dropwise to 10ml of N,N-dimethylsulfoxide at 0°C. After the dropwise addition is complete, raise the temperature and control the temperature at 55°C to 60°C for 0.5h. TLC detects that the reaction is completed, and 50ml of dichloromethane is added to the reaction solution, and then 10ml of saturated NaCl is added to the reaction solution. 2 S 2 o3 solution, the organic layer was washed with saturated NaCl solution (20ml*3), the organic layer was dried with anhydrous magnesium sulfate, filtered, the filtrate was concentrated under reduced pressure, and separated by column chromatography [eluent: dichloromethane: methanol: glacial acetic acid = 30 :1:1] to obtain 1.38g of white solid, that is, compound 2, with a yield of 31.6% and a liquid phase purity of 99.2%.
[0047] The...
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