Synthesis of cephalosporin compounds
Provided herein is a method for the synthesis of cephalosporin antibiotic compounds comprising a palladium-catalyzed coupling reaction. Provided herein are methods for the synthesis of cephalosporin compounds of formula (I) employing a palladium-catalyzed alkylation reaction, as well as compositions related to the same. In an aspect, provided herein is a method for preparing a compound of formula (II), or a salt thereof, comprising the step of admixing, e.g., reacting, a compound of formula (III), or a salt thereof, with a nucleophile (Nuc) in the presence of reagents comprising: (a) a palladium source; and (b) a palladium-binding ligand, to form a compound of formula (II), or a salt thereof.
1. A composition comprising a compound of formula (Va):
and from about 0.01 ppm to about 5 ppm palladium,
wherein A ⊖ is a pharmaceutically acceptable anion selected from chloride, bromide, iodide, sulfate, bisulfate, toluenesulfonate, methanesulfonate, edisylate, maleate, phosphate, ketoglutarate, acetate, trifluoroacetate, and trifluoromethanesulfonate.
2. The composition of claim 1 , which comprises from about 0.01 ppm to about 3 ppm palladium.
3. The composition of claim 1 , which comprises from about 0.01 ppm to about 2 ppm palladium.
4. The composition of claim 1 , which comprises from about 0.01 ppm to about 1 ppm palladium.
5. The composition of claim 1 , wherein A ⊖ is chloride.
6. The composition of claim 1 , wherein A ⊖ is bisulfate.
7. The composition of claim 1 , wherein A ⊖ is acetate.
8. The composition of claim 1 , wherein A ⊖ is trifluoroacetate.
9. A composition comprising a compound of formula (VII):
and from about 0.01 ppm to about 5 ppm palladium.
10. The composition of claim 9 , which comprises from about 0.01 ppm to about 3 ppm palladium.
11. The composition of claim 9 , which comprises from about 0.01 ppm to about 2 ppm palladium.
12. The composition of claim 9 , which comprises from about 0.01 ppm to about 1 ppm palladium.
13. A composition comprising a compound of formula (VII):
and from about 0.01 ppm to about 1 ppm palladium.