반응 #5621

반응 방정식

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

용매

N,N-dimethylformamide

반응 조건

후처리

1. 1
   여과The resulting precipitate was collected by filtration
2. 2
   세척washed 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
   온도cooling
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
   여과The resultant precipitate was collected by filtration
10. 10
    workup.DISSOLUTIONdissolved in aqueous sodium bicarbonate
11. 11
    기타" (Trademark:prepared by Mitsubishi Chemical Industries) with 5% aqueous isopropyl alcohol as an eluent

실험 절차

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).

출처