반응 #64293

반응 방정식

PCl5

7-amino-3-[2-(3,4-dihydroxyphenyl)-1,3,4-thiadiazol-5-ylthiomethyl]ceph-3-em-4-carboxylic acid

bistrimethylsilylacetamide

(Z)-ethoxyimino-2-(tritylaminothiazol-4-yl) acetic acid chloride

→

title compound

수율 7.0%

7-[2-(2-Aminothiazol-4-yl )-2-((Z)-ethoxyimino)acetamido]-3-[2-(3,4-dihydroxyphenyl)-1,3,4-thiadiazol-5-ylthiomethyl]ceph-3-em-4-carboxylic acid

수율 7.0%

용매

dichloromethane

dichloromethane

반응 조건

후처리

1. 1
   기타followed by evaporation of the solvent
2. 2
   workup.WAITAfter a few minutes at 0° C.
3. 3
   기타the solvent was evaporated
4. 4
   기타all the protecting groups removed
5. 5
   workup.ADDITIONby treating the crude
6. 6
   기타reaction mixture with TFA/water for 1 hour at room temperature
7. 7
   기타The solvents were evaporated
8. 8
   workup.DISSOLUTIONthe crude product dissolved in MeOH
9. 9
   기타precipitated in ether
10. 10
    기타Further purification

실험 절차

1 equivalent of 7-amino-3-[2-(3,4-dihydroxyphenyl)-1,3,4-thiadiazol-5-ylthiomethyl]ceph-3-em-4-carboxylic acid was silylated with 4 equivalents of bistrimethylsilylacetamide in anhydrous dichloromethane at room temperature for three hours. To this solution, cooled to 0° C. under argon, was added 1 equivalent of 2-[(Z)-ethoxyimino-2-(tritylaminothiazol-4-yl) acetic acid chloride (prepared from the corresponding acid (1 equivalent), 1 equivalent PCl5 and 1 equivalent TEA in dichloromethane at 0° C. for 2 hours followed by evaporation of the solvent and all POCl3, and redissolution in dichloromethane). After a few minutes at 0° C., the solvent was evaporated, and all the protecting groups removed by treating the crude reaction mixture with TFA/water for 1 hour at room temperature. The solvents were evaporated and the crude product dissolved in MeOH and precipitated in ether. Further purification was achieved by MPLC, to yield the title compound (7%), NMR (DMSOd6, AcOD, TFA), 1.25 (t,3H); 3.7 (m,2H); 4.2 and 4.25 (2d,2H); 4.4 (q,2H); 5.15 (d,1H); 5.75 (d,1H); 6.85 (d,1H); 7 (s,1H); 7.15 (d,1H); 7.3 (s,1H).

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