反応 #214278

反応方程式

3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-7-amino-3-cephem-4-carboxylic acid

trimethylsilylacetamide

sodium chloride

phosphorus pentachloride

2-(3-methylureido)thiazol-4-ylacetic acid

→

3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-7-[2-(3-methylureido)thiazol-4-yl]acetamido-3-cephem-4-carboxylic acid

収率 40.6%

溶媒

ethyl acetate

methylene chloride

ethyl acetate

methylene chloride

反応条件

後処理

1. 1
   温度cooling
2. 2
   workup.STIRRINGthe mixture was stirred for 3 hours under ice-
3. 3
   温度cooling
4. 4
   ろ過The precipitates were collected by filtration
5. 5
   洗浄washed with n-hexane
6. 6
   その他Thus obtained
7. 7
   その他precipitates
8. 8
   workup.ADDITIONwere added to a solution which
9. 9
   その他was prepared
10. 10
    workup.STIRRINGby stirring
11. 11
    workup.STIRRINGThe mixture was stirred for 1 hour at -20° to -10° C.
12. 12
    workup.STIRRINGfurther stirred for 1 hour at -10° to 0° C
13. 13
    workup.ADDITIONwas added therto, and then the mixture
14. 14
    workup.STIRRINGstirred for 10 minutes at room temperature
15. 15
    その他was separated out
16. 16
    その他the remaining precipitates
17. 17
    洗浄were washed with ethyl acetate (50 ml.)
18. 18
    workup.ADDITIONTo the precipitates was added water (30 ml.)
19. 19
    workup.STIRRINGwith stirring under ice-
20. 20
    温度cooling
21. 21
    ろ過The precipitates were collected by filtration
22. 22
    乾燥dried over phosphorus pentachloride under reduced pressure

実験手順

To a mixture of 2-(3-methylureido)thiazol-4-ylacetic acid (3.23 g.) in dried methylene chloride (50 ml.) was dropwise added a solution of phosphorus pentachloride in dried methylene chloride (80 ml.) with stirring under ice-cooling, and the mixture was stirred for 3 hours under ice-cooling. The precipitates were collected by filtration and washed with n-hexane. Thus obtained precipitates were added to a solution which was prepared by stirring a mixture of 3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-7-amino-3-cephem-4-carboxylic acid (4.95 g.) and trimethylsilylacetamide (11.8 g.) in dried ethyl acetate (75 ml.) for 10 minutes at 40° C. and then by cooling it to at -20° C. The mixture was stirred for 1 hour at -20° to -10° C. and further stirred for 1 hour at -10° to 0° C. The mixture was cooled to at -20° C., and 10% aqueous solution of sodium chloride (7 ml.) was added therto, and then the mixture stirred for 10 minutes at room temperature. After the reaction, ethyl acetate layer was separated out, and the remaining precipitates were washed with ethyl acetate (50 ml.). To the precipitates was added water (30 ml.) and adjusted to pH 5 to 6 with sodium bicarbonate powder with stirring under ice-cooling. Thus obtained solution was subjected to alumina column chromatography, and the eluate was adjusted pH 2 with 17.5% hydrochloric acid. The precipitates were collected by filtration and dried over phosphorus pentachloride under reduced pressure to give white powder of 3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-7-[2-(3-methylureido)thiazol-4-yl]acetamido-3-cephem-4-carboxylic acid (3.20 g.)

出典