Preparation method of two etoposide impurities
A technology for etoposide and impurities, which is applied in the field of drug synthesis, can solve problems such as the chiral situation is not clearly given, the content is small, and the specific operation of compound synthesis is not given, and the route design is reasonable, the raw materials are easy to obtain, and the raw materials cheap effect
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Embodiment 1
[0036] Take 8.00g of tert-butyldimethylsilyl-protected 4'-demethyl epipodophyllotoxin in tetrahydrofuran, add 6.29g of tributylphosphine and 9.15g of etoposide, and then add 6.29g of Diisopropyl azodicarboxylate, the mixture was reacted at 40°C for 8 hours, thin-layer chromatography showed that the reaction was complete, the reaction solution was concentrated to remove tetrahydrofuran, and purified on a silica gel column to obtain 12.50 g of compound C with a yield of 74.10%; MS: 1107.3 [M +Na] + .
[0037]
[0038] (2) Dissolve 10.0 g of compound C in 100 mL of tetrahydrofuran, add 4.82 g of tetrabutylammonium fluoride, and react at 30 ° C for 2 hours. Thin layer chromatography shows that the reaction is complete. After adding water to separate the organic phase, purify on a silica gel column Obtained 7.21g of compound D, yield 80.74%; MS: 993.3[M+Na] + , NMR see attached figure 2 ;
[0039]
[0040] (3) Dissolve 5.00 g of compound D in 50 mL of 1,4-dioxane, add 25...
Embodiment 2
[0043] (1) Take 10.0g of tert-butyldimethylsilyl-protected 4'-demethyl epipodophyllotoxin in tetrahydrofuran, add 7.64g of triphenylphosphine and 11.44g of etoposide, then add 5.08 g of diisopropyl azodicarboxylate, the mixed solution was reacted at 40°C for 8 hours, thin-layer chromatography showed that the reaction was complete, the reaction solution was concentrated to remove tetrahydrofuran, and purified on a silica gel column to obtain 18.40 g of compound C with a yield of 87.26%, MS :1107.3[M+Na] + .
[0044]
[0045] (2) Dissolve 5.00 g of compound C in 60 mL of tetrahydrofuran, add 3.31 g of 70% pyridine hydrogen fluoride solution, and react at 30° C. for 3 hours. Thin layer chromatography shows that the reaction is complete. After adding water to separate the organic phase, purify on a silica gel column Obtain 3.90g of compound D, yield 87.18%; MS:993.3[M+Na], 1 H-NMR is the same as embodiment 1;
[0046]
[0047] (3) Dissolve 3.00 g of compound D in 100.0 mL o...
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