Reaktion #55422

Reaktionsgleichung

lead dioxide

7-amino-3-[1-(2-carbamoylethyl)tetrazol-5-ylthiomethyl]-3-cephem-4-carboxylic acid t-butyl ester

3,5-di-t-butyl-4-hydroxybenzaldehyde

benzene

→

7β-amino-7α-methoxy-3-[1-(2-carbamoylethyl)tetrazol-5-ylthiomethyl]-3-cephem-4-carboxylic acid t-butyl ester

Lösungsmittel

water

1,2-dichloroethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe solution is evaporated uner reduced pressure
2. 2
   Sonstigeto give a residue which
3. 3
   workup.DISSOLUTIONis dissolved in 150 ml
4. 4
   Sonstigecold until complete consumption of starting material
5. 5
   FiltrationThe mixture is then filtered through Celite
6. 6
   Waschenthe filter cake is washed with two 30 ml
7. 7
   workup.ADDITIONThe filtrate is treated with 30 ml
8. 8
   workup.STIRRINGof dry methanol (distilled from magnesium) and the reaction mixture is stirred at ambient temperature until complete consumption of the intermediate and formation of a new product
9. 9
   SonstigeThe reaction mixture is evaporated to dryness
10. 10
    workup.ADDITIONof methanol and treated with 4.0 g
11. 11
    workup.STIRRINGThis solution is stirred at ambient temperature for 3 hours
12. 12
    Sonstigeevaporated under vacuum to a solid residue
13. 13
    Sonstigepartitioned between 150 ml
14. 14
    WaschenThe organic phase is washed with three 100 ml
15. 15
    TrocknenThe organic phase is dried (MgSO4)
16. 16
    Filtrationfiltered
17. 17
    Sonstigeevaporated to dryness

Vorschrift

A solution of 1.76 g. (4 mmol.) of 7-amino-3-[1-(2-carbamoylethyl)tetrazol-5-ylthiomethyl]-3-cephem-4-carboxylic acid t-butyl ester and 0.94 g. (4 mmol.) of 3,5-di-t-butyl-4-hydroxybenzaldehyde in 150 ml. of dry benzene is refluxed for ca. 4 hours under a Dean-Stark trap until no more water separates. The solution is evaporated uner reduced pressure to give a residue which is dissolved in 150 ml. of 1,2-dichloroethane and cooled to 0°-5° in an ice bath. Freshly prepared lead dioxide (5 g.) is added in 1 g. portions over 30 minutes and the reaction is stirred in the cold until complete consumption of starting material is shown by thin layer chromatography. The mixture is then filtered through Celite and the filter cake is washed with two 30 ml. portions of cold 1,2-dichloroethane. The filtrate is treated with 30 ml. of dry methanol (distilled from magnesium) and the reaction mixture is stirred at ambient temperature until complete consumption of the intermediate and formation of a new product are shown by thin layer chromatography. The reaction mixture is evaporated to dryness and the residue is taken up in 50 m. of methanol and treated with 4.0 g. of Girard reagent T. This solution is stirred at ambient temperature for 3 hours, evaporated under vacuum to a solid residue and partitioned between 150 ml. of ethyl acetate and 100 ml. of 20% aqueous sodium chloride solution. The organic phase is washed with three 100 ml. portions of 10% aqueous sodium chloride, two 100 ml. portions of water and 100 ml. of 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-carbamoylethyl)tetrazol-5-ylthiomethyl]-3-cephem-4-carboxylic acid t-butyl ester.

Quelle