Reaktion #56562

Reaktionsgleichung

2-methyl-7-amino-3-cephem-4-carboxylic acid

bis(trimethylsilyl)acetamide

2-(2-formylaminothiazol-4-yl)glyoxylic acid

phosphorus oxychloride

sodium bicarbonate

2-(2-formylimino-2,3-dihydrothiazol-4-yl)glyoxylic acid

→

2-methyl-7-[2-(2-formylaminothiazol-4-yl)glyoxylamido]-3-cephem-4-carboxylic acid

Lösungsmittel

methylene chloride

dimethylformamide

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturice-cooling
2. 2
   workup.STIRRINGthe mixture was stirred for 30 minutes at 40° C
3. 3
   workup.STIRRINGthe mixture was stirred for 30 minutes
4. 4
   Temperaturunder cooling at -20° to -15° C
5. 5
   workup.ADDITIONThus obtained mixture was added to a solution, which
6. 6
   Sonstigewas prepared
7. 7
   workup.STIRRINGby stirring
8. 8
   Temperaturunder cooling at -50° to -45° C.
9. 9
   workup.STIRRINGwith stirring
10. 10
    workup.STIRRINGThe mixture was stirred for 1 hour at -45° to -40° C.
11. 11
    workup.STIRRINGwith shaking
12. 12
    SonstigeThe aqueous layer was separated
13. 13
    Waschenwashed with ethyl acetate
14. 14
    SonstigeThe ethyl acetate layer was separated from the mixture
15. 15
    Extraktionthe remaining aqueous layer was extracted with ethyl acetate (200 ml.×2)
16. 16
    Waschenwashed with water
17. 17
    Einengenconcentrated to a small volume
18. 18
    FiltrationThe precipitates were collected by filtration
19. 19
    Waschenwashed with a small amount of ethyl acetate
20. 20
    Sonstigedried

Vorschrift

To dimethylformamide (78 ml.) was added dropwise phosphorus oxychloride (11.9 g.) under stirring and ice-cooling, and the mixture was stirred for 30 minutes at 40° C. To the mixture was added 2-(2-formylaminothiazol-4-yl)glyoxylic acid, which can be represented as 2-(2-formylimino-2,3-dihydrothiazol-4-yl)glyoxylic acid, (7.8 g.) under cooling at -20° C., and then the mixture was stirred for 30 minutes under cooling at -20° to -15° C. Thus obtained mixture was added to a solution, which was prepared by stirring a mixture of 2-methyl-7-amino-3-cephem-4-carboxylic acid (8.35 g.) and bis(trimethylsilyl)acetamide (19.5 ml.) in dried methylene chloride (170 ml.) at room temperature, under cooling at -50° to -45° C. with stirring. The mixture was stirred for 1 hour at -45° to -40° C. and then the reaction mixture was poured into a solution of sodium bicarbonate (32 g.) in water (1.5 l) with shaking. The aqueous layer was separated and washed with ethyl acetate. The aqueous solution was layered with ethyl acetate and then adjusted to pH 1 to 2 with concentrated hydrochloric acid. The ethyl acetate layer was separated from the mixture, and the remaining aqueous layer was extracted with ethyl acetate (200 ml.×2). The ethyl acetate layers were combined together, washed with water and then concentrated to a small volume. The precipitates were collected by filtration, washed with a small amount of ethyl acetate and then dried to give 2-methyl-7-[2-(2-formylaminothiazol-4-yl)glyoxylamido]-3-cephem-4-carboxylic acid, which can be represented as 2-methyl-7-[2-(2-formylimino-2,3-dihydrothiazol-4-yl)glyoxylamido]-3-cephem-4-carboxylic acid, (7.9 g.), mp 210° to 215° C. (dec.).

Quelle