反応 #56562

反応方程式

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

溶媒

methylene chloride

dimethylformamide

water

反応条件

後処理

1. 1
   温度ice-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
   温度under cooling at -20° to -15° C
5. 5
   workup.ADDITIONThus obtained mixture was added to a solution, which
6. 6
   その他was prepared
7. 7
   workup.STIRRINGby stirring
8. 8
   温度under 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
    その他The aqueous layer was separated
13. 13
    洗浄washed with ethyl acetate
14. 14
    その他The ethyl acetate layer was separated from the mixture
15. 15
    抽出the remaining aqueous layer was extracted with ethyl acetate (200 ml.×2)
16. 16
    洗浄washed with water
17. 17
    濃縮concentrated to a small volume
18. 18
    ろ過The precipitates were collected by filtration
19. 19
    洗浄washed with a small amount of ethyl acetate
20. 20
    その他dried

実験手順

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.).

出典