Reaktion #5621

Reaktionsgleichung

ethyl acetate

7β-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetamido]-3-chloromethyl-3-cephem-4-carboxylic acid trifluoroacetate

1-methyl-4-tert-butoxycarbonylpiperazine

→

7β-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetamido]-3-(1-methyl-1-piperazinio)methyl-3-cephem-4-carboxylate

Lösungsmittel

N,N-dimethylformamide

Reaktionsbedingungen

Aufarbeitung

1. 1
   FiltrationThe resulting precipitate was collected by filtration
2. 2
   Waschenwashed with ethyl acetate and diisopropyl ether
3. 3
   workup.ADDITIONTo a solution of the above precipitate in a mixture of methylene chloride (6e ml) and anisole (20 ml)
4. 4
   workup.ADDITIONwas added dropwise trifluoroacetic acid (40 ml) under ice-
5. 5
   Temperaturcooling
6. 6
   workup.STIRRINGThe reaction mixture was stirred at room temperature for 2 hours
7. 7
   workup.ADDITIONadded to diisopropyl ether (1.5 l)
8. 8
   workup.STIRRINGunder stirring
9. 9
   FiltrationThe resultant precipitate was collected by filtration
10. 10
    workup.DISSOLUTIONdissolved in aqueous sodium bicarbonate
11. 11
    Sonstige" (Trademark:prepared by Mitsubishi Chemical Industries) with 5% aqueous isopropyl alcohol as an eluent

Vorschrift

To a solution of 7β-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetamido]-3-chloromethyl-3-cephem-4-carboxylic acid trifluoroacetate (syn isomer) in N,N-dimethylformamide (150 ml) was added 1-methyl-4-tert-butoxycarbonylpiperazine (30 g). After being stirred at room temperature for 30 minutes, the mixture was added dropwise to ethyl acetate (1.5 l). The resulting precipitate was collected by filtration, washed with ethyl acetate and diisopropyl ether. To a solution of the above precipitate in a mixture of methylene chloride (6e ml) and anisole (20 ml) was added dropwise trifluoroacetic acid (40 ml) under ice-cooling. The reaction mixture was stirred at room temperature for 2 hours and added to diisopropyl ether (1.5 l) under stirring. The resultant precipitate was collected by filtration and dissolved in aqueous sodium bicarbonate, and the solution was adjusted to pH 4.0 with hydrochloric acid and subjected to column chromatography on "Diaion HP-20" (Trademark:prepared by Mitsubishi Chemical Industries) with 5% aqueous isopropyl alcohol as an eluent. The eluate was lyophilized to give 7β-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetamido]-3-(1-methyl-1-piperazinio)methyl-3-cephem-4-carboxylate (syn isomer) (12.00 g).

Quelle