反应详情

温度

0 °C

Thionyl chloride (8.7 g.) is added to a solution of (5,6-dihydro-1,4-dithiin-2-yl)acetic acid (6.45 g.) in benzene (120 cc.). The mixture is heated under reflux until gas ceases to be evolved and is then concentrated to dryness under reduced pressure (20 mm.Hg). The brown oil thus obtained is dissolved in acetone (50 cc.) and the resulting solution is added dropwise, over the course of one hour, to a solution of 7-amino-2-carboxy-3-[(1-methyl-1,2,3,4-tetrazol-5-yl)thiomethyl]-8-oxo-5-thia-1-aza-bicyclo[4,2,0]oct-2-ene (12 g.) and sodium bicarbonate (7.35 g.) in water (200 cc.) and acetone (100 cc.) kept at 3° C. Stirring is continued for a further hour at 3° C. and then for 2 hours at about 20° C. The mixture is concentrated to dryness under reduced pressure (20 mm.Hg), water (150 cc.) is added and the slight amount of insoluble matter is filtered off. The solution is washed twice with ethyl acetate (300 cc.) and brought to pH 2.2 by addition of 4 N hydrochloric acid in the presence of ethyl acetate (300 cc.). The solution is filtered through "Supercel" and decanted, and the aqueous phase is extracted with ethyl acetate (300 cc.). The organic phases are combined and washed with water (200 cc.), dried over magnesium sulphate and treated with decolourizing charcoal. The mixture is filtered and the filtrate is concentrated to a volume of 100 cc. Diethyl ether (700 cc.) is then added and the mixture is cooled to about 0° C.; the resulting precipitate is filtered off and washed with diethyl ether (100 cc.). 2-Carboxy-7-[(5,6-dihydro-1,4-dithiin-2-yl)-acetamido]-3-[(1-methyl-1,2,3,4-tetrazol-5-yl)thiomethyl]-8-oxo-5-thia-1-aza-bicyclo[4,2,0]oct-2-ene (4.4 g.) is obtained in the form of a cream powder.

1. temperatureThe mixture is heated
2. temperatureunder reflux until gas ceases
3. concentrationis then concentrated to dryness under reduced pressure (20 mm.Hg)
4. customThe brown oil thus obtained
5. customkept at 3° C
6. waitis continued for a further hour at 3° C.
7. concentrationThe mixture is concentrated to dryness under reduced pressure (20 mm.Hg), water (150 cc.)
8. additionis added
9. filtrationthe slight amount of insoluble matter is filtered off
10. washThe solution is washed twice with ethyl acetate (300 cc.)
11. additionbrought to pH 2.2 by addition of 4 N hydrochloric acid in the presence of ethyl acetate (300 cc.)
12. filtrationThe solution is filtered through "Supercel"
13. customdecanted
14. extractionthe aqueous phase is extracted with ethyl acetate (300 cc.)
15. washwashed with water (200 cc.)
16. dry with materialdried over magnesium sulphate
17. additiontreated with decolourizing charcoal
18. filtrationThe mixture is filtered
19. concentrationthe filtrate is concentrated to a volume of 100 cc
20. additionDiethyl ether (700 cc.) is then added
21. filtrationthe resulting precipitate is filtered off
22. washwashed with diethyl ether (100 cc.)