反応 #214276

反応方程式

2-methanesulfonamidothiazol-5-ylacetic acid

sodium bicarbonate

sodium bicarbonate

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

phosphorus pentachloride

→

3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-7-(2-methanesulfonamidothiazol-5-yl)acetamido-3-cephem-4-carboxylic acid

収率 45.8%

溶媒

diethyl ether

methylene chloride

acetone

acetone

water

n-hexane

反応条件

後処理

1. 1
   温度cooling
2. 2
   workup.STIRRINGthe mixture was stirred for 30 minutes at the same temperature
3. 3
   洗浄the precipitated crystals were washed by decantation three times
4. 4
   workup.ADDITIONThus obtained crystals were gradually added to a solution, which
5. 5
   その他is prepared
6. 6
   温度by cooling it at 0° to 5° C.
7. 7
   温度under ice-cooling
8. 8
   workup.STIRRINGstirring while the mixture
9. 9
   workup.STIRRINGThe mixture was further stirred for 40 minutes at about the same pH and temperature
10. 10
    その他was removed
11. 11
    洗浄by washing the reaction mixture with benzene
12. 12
    ろ過filtered
13. 13
    温度cooling
14. 14
    その他The ethyl acetate layer was separated from the mixture
15. 15
    抽出the remaining aqueous layer was extracted twice with ethyl acetate (70 ml.)
16. 16
    洗浄washed with water
17. 17
    乾燥a saturated sodium chloride aqueous solution in turn and then dried over magnesium sulfate
18. 18
    workup.DISTILLATIONThe solvent was distilled off from the ethyl acetate layer
19. 19
    その他the resulting yellow powder was dried

実験手順

To a mixture of 2-methanesulfonamidothiazol-5-ylacetic acid (1.65 g.), dried methylene chloride (40 ml.) and diethyl ether (4 ml.) was added phosphorus pentachloride (3.5 g.) under ice-cooling and stirring and the mixture was stirred for 30 minutes at the same temperature. To the mixture was added n-hexane, and the precipitated crystals were washed by decantation three times. Thus obtained crystals were gradually added to a solution, which is prepared by adding sodium bicarbonate (2.15 g.) to a suspension of 3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-7-amino-3-cephem-4-carboxylic acid (2.1 g.) in a mixture of acetone (25 ml.) and water (25 ml.) and then by cooling it at 0° to 5° C., under ice-cooling and stirring while the mixture was kept to pH 7.5 to 8 with a saturated sodium bicarbonate aqueous solution. The mixture was further stirred for 40 minutes at about the same pH and temperature. After the reaction, acetone was removed by washing the reaction mixture with benzene. The aqueous layer was adjusted to pH 5 with 5% hydrochloric acid and filtered. To the aqueous filtrate was overlayed ethyl acetate, and the mixture was gradually adjusted to pH 2 with 5% hydrochloric acid under ice-cooling. The ethyl acetate layer was separated from the mixture, and the remaining aqueous layer was extracted twice with ethyl acetate (70 ml.). The ethyl acetate layers were combined together, washed with water and a saturated sodium chloride aqueous solution in turn and then dried over magnesium sulfate. The solvent was distilled off from the ethyl acetate layer, and the resulting yellow powder was dried to give a mixture (1.6 g.) of 3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-7-(2-methanesulfonamidothiazol-5-yl)acetamido-3-cephem-4-carboxylic acid (hereinafter referred to Amino compound) and 3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-7-(2-methanesulfonimido-2,3-dihydrothiazol-5-yl)acetamido-3-cephem-4-carboxylic acid (hereinafter referred to Imino compound).

出典