反应 #4868

反应方程式

7β-amino-3-(1-pyridiniomethyl)-3-cephem-4-carboxylate

(Z)-2-(2-tritylaminothiazol-4-yl)-2-[(2-pyrrolidon-3-yl)oxyimino]acetic acid

N,O-bis(trimethylsilyl)acetamide

dihydrochloride

oxalyl chloride

→

7β-{(Z)-2-(2-aminothiazol-4-yl)-2-[(2-pyrrolidon-3-yl)oxyimino]acetamido}-3-(1-pyridiniomethyl)-3-cephem-4-carboxylate

溶剂

water

chloroform

triethylamine

chloroform

chloroform

dimethylformamide

chloroform

反应条件

后处理

1. 1
   其他at -30° C
2. 2
   workup.STIRRINGThe mixture is stirred at the same temperature for 5 minutes
3. 3
   其他is prepared
4. 4
   workup.DISSOLUTIONto dissolve
5. 5
   workup.ADDITION) is added to the said mixture at -30° to -10° C
6. 6
   workup.STIRRINGAfter the mixture is stirred at the same temperature for 30 minutes
7. 7
   浓缩is concentrated to dryness under reduced pressure
8. 8
   workup.ADDITION100 ml of 80% aqueous formic acid are added to the residue
9. 9
   workup.STIRRINGis stirred at room temperature for one hour
10. 10
    workup.ADDITION100 ml of water are added to the mixture, and insoluble materials
11. 11
    过滤are filtered off
12. 12
    洗涤The filtrate is washed with ethyl acetate
13. 13
    浓缩is concentrated to dryness under reduced pressure
14. 14
    其他The residue thus obtained
15. 15
    其他chromatographed on a column of non-ionic polymer resin Diaion
16. 16
    洗涤The column is washed with water
17. 17
    洗涤followed by elution with 20% aqueous methanol
18. 18
    workup.ADDITIONThe fractions containing the cephalosporin compound
19. 19
    其他are collected
20. 20
    浓缩concentrated to dryness under reduced pressure
21. 21
    workup.ADDITIONAcetone is added to the residue
22. 22
    过滤the resulting powder is collected by filtration

实验过程

1.56 g of oxalyl chloride are added at -5° to 0° C. to 39 ml of chloroform containing 0.99 ml of dimethylformamide, and the mixture is stirred at the same temperature for 15 minutes. A solution of 4.23 g of (Z)-2-(2-tritylaminothiazol-4-yl)-2-[(2-pyrrolidon-3-yl)oxyimino]acetic acid (d-isomer) and 0.84 g of triethylamine in 39 ml of chloroform is added to said mixture at -30° C. The mixture is stirred at the same temperature for 5 minutes. Then, a solution of 7β-amino-3-(1-pyridiniomethyl)-3-cephem-4-carboxylate in chloroform (said solution is prepared by suspending 5.0 g of the dihydrochloride of said cephem compound in 39 ml of chloroform and adding 11 ml of N,O-bis(trimethylsilyl)acetamide thereto to dissolve said salt therein) is added to the said mixture at -30° to -10° C. After the mixture is stirred at the same temperature for 30 minutes, said mixture is concentrated to dryness under reduced pressure. 100 ml of 80% aqueous formic acid are added to the residue, and said aqueous mixture is stirred at room temperature for one hour. 100 ml of water are added to the mixture, and insoluble materials are filtered off. The filtrate is washed with ethyl acetate and is concentrated to dryness under reduced pressure. The residue thus obtained is dissolved in water and chromatographed on a column of non-ionic polymer resin Diaion HP-20 (resistered trade mark, manufactured by Mitsubishi Chemical Industries Ltd., Japan). The column is washed with water, followed by elution with 20% aqueous methanol. The fractions containing the cephalosporin compound are collected and concentrated to dryness under reduced pressure. Acetone is added to the residue, and the resulting powder is collected by filtration. 2.14 g of 7β-{(Z)-2-(2-aminothiazol-4-yl)-2-[(2-pyrrolidon-3-yl)oxyimino]acetamido}-3-(1-pyridiniomethyl)-3-cephem-4-carboxylate (d-isomer) are obtained. Another designation of this dextrorotatory isomer is shown as 7β-{(Z)-2-(2-aminothiazol-4-yl)-2-[((3R)-2-pyrrolidon-3-yl)oxyimino]acetamido}-3-(1-pyridiniomethyl)-3-cephem-4-carboxylate.

来源