반응 #56562

반응 방정식

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

용매

methylene chloride

dimethylformamide

water

반응 조건

후처리

1. 1
   온도ice-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
   온도under cooling at -20° to -15° C
5. 5
   workup.ADDITIONThus obtained mixture was added to a solution, which
6. 6
   기타was prepared
7. 7
   workup.STIRRINGby stirring
8. 8
   온도under 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
    기타The aqueous layer was separated
13. 13
    세척washed with ethyl acetate
14. 14
    기타The ethyl acetate layer was separated from the mixture
15. 15
    추출the remaining aqueous layer was extracted with ethyl acetate (200 ml.×2)
16. 16
    세척washed with water
17. 17
    농축concentrated to a small volume
18. 18
    여과The precipitates were collected by filtration
19. 19
    세척washed with a small amount of ethyl acetate
20. 20
    기타dried

실험 절차

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.).

출처