Réaction #334051

Équation de réaction

diisopropylethylamine

sulbactam sodium salt

chlorobromomethane

→

sulbactam

Rendement 84.0%

Conditions de réaction

Traitement

1. 1
   Extractionthe reaction mixture was extracted with 3×100 ml of water
2. 2
   workup.ADDITIONdiluted with 100 ml fresh ethyl acetate
3. 3
   Extractionextracted 1×275 ml H2O, 1×275 ml saturated Na2SO4, 1×275 H2O and 1×275 ml brine
4. 4
   Séchagedried over 20 g MgSO 4
5. 5
   Filtrationfiltered over diatomaceous earth with 100 ml of ethyl acetate
6. 6
   Lavagewash
7. 7
   LavageThe filtrate and wash liquor
8. 8
   Températurecooled to 0°-5° C.
9. 9
   workup.ADDITIONdiluted dropwise with 90 ml of hexane
10. 10
    Températuremaintaining 0°-5° C. (
11. 11
    workup.ADDITIONdiluted dropwise over 1.5 hours with 150 ml of additional hexane
12. 12
    Températurecooled
13. 13
    workup.WAITgranulated at 0°-5° C. for 1 hour
14. 14
    Autretitle product recovered in two crops (the
15. 15
    Autreevaporation of the mother liquor and trituration with hexane), 13.8 g and 4.7 g

Mode opératoire

The tetrabutylammonium salt of sulbactam (53 g of an oil) was prepared from sulbactam sodium salt (20.0 g, 0.078 mol) and tetrabutylammonium hydrogen sulfate (33.2 g) according to the method of Example 1. The entire 53 g batch was taken into 1280 ml of chlorobromomethane containing 1.70 ml (0.0098 mol) of diisopropylethylamine. After 5 hours, the reaction mixture was extracted with 3×100 ml of water. By optical rotation assay, the first, second and third extracts contained 5.7%, 1.1% and 0.3% of recovered sulbactam. The organic layer was stripped to a volume of 300 ml, and the BrCH2Cl displaced with 2×500 ml of ethyl acetate to a final volume of 275 ml, diluted with 100 ml fresh ethyl acetate, extracted 1×275 ml H2O, 1×275 ml saturated Na2SO4, 1×275 H2O and 1×275 ml brine, dried over 20 g MgSO 4, stirred with 4 g of activated carbon for 30 minutes, and filtered over diatomaceous earth with 100 ml of ethyl acetate wash. The filtrate and wash liquor were combined, stripped to 100 ml, cooled to 0°-5° C., diluted dropwise with 90 ml of hexane, maintaining 0°-5° C. (leading to an oil), warmed back to ambient temperature (causing the oil to form crystals), diluted dropwise over 1.5 hours with 150 ml of additional hexane, cooled and granulated at 0°-5° C. for 1 hour, and title product recovered in two crops (the second following evaporation of the mother liquor and trituration with hexane), 13.8 g and 4.7 g, both melting at 89°-95° C., a yield of 84% uncorrected, a yield of 80% corrected for purity by hplc.

Source