反应详情

A solution of 1.18 g (2.4 mmol) of 7β-amino-3-[1-(2-methanesulfonamidoethyl)tetrazol-5-ylthiomethyl]-3-cephem-4-carboxylic acid t-butyl ester and 0.56 g (2.4 mmol) of 3,5-di-t-butyl-4-hydroxybenzaldehyde in 100 ml of dry benzene is refluxed for 4 hours under a Dean-Stark trap. The solution is evaporated under reduced pressure to leave a residue which is dissolved in 100 ml of 1,2-dichloroethane and cooled to ca. 5° in an ice bath. Three grams of freshly prepared lead dioxide is added in portions over 20 minutes until the starting material is completely consumed. The mixture is filtered through Celite and the filter cake is washed with two 20 ml portions of cold 1,2-dichloroethane. The filtrate is treated with 25 ml of methanol (distilled from magnesium) and the reaction mixture is allowed to stand at room temperature until complete consumption of the oxidized intermediate and formation of a new slower-moving product is shown by thin layer chromatography. The mixture is evaporated and the residue is dissolved in 30 ml of methanol and treated with 2.5 g of Girard reagent T (trimethylaminoacetohydrazide chloride). The reaction mixture is stirred at room temperature for 3 hours, then evaporated to give a residue which is partitioned between ethyl acetate and 20% sodium chloride solution. The organic phase is washed with 10% sodium chloride solution water and a saturated sodium chloride solution. The organic phase is dried (MgSO4), filtered and evaporated to dryness to give 7β-amino-7α-methoxy-3-[1-(2-methanesulfonamidoethyl)tetrazol-5-ylthiomethyl]-3-cephem-4-carboxylic acid t-butyl ester.

1. customThe solution is evaporated under reduced pressure
2. customto leave a residue which
3. temperaturecooled to ca. 5° in an ice bath
4. customis completely consumed
5. filtrationThe mixture is filtered through Celite
6. washthe filter cake is washed with two 20 ml portions of cold 1,2-dichloroethane
7. additionThe filtrate is treated with 25 ml of methanol (distilled from magnesium)
8. customto stand at room temperature until complete consumption of the oxidized intermediate and formation of a new slower-moving product
9. customThe mixture is evaporated
10. dissolutionthe residue is dissolved in 30 ml of methanol
11. additiontreated with 2.5 g of Girard reagent T (trimethylaminoacetohydrazide chloride)
12. customevaporated
13. customto give a residue which
14. customis partitioned between ethyl acetate and 20% sodium chloride solution
15. washThe organic phase is washed with 10% sodium chloride solution water
16. dry with materialThe organic phase is dried (MgSO4)
17. filtrationfiltered
18. customevaporated to dryness