Improved Synthesis of Cefdinir and Its Polymorphic Form, an Antibacterial Active Pharmaceutical Ingredient

Abstract

New methods for the preparation of Cefdinir 1 and its polymorphic form Sesqui hydrate 1a are described. The synthesis of 2‐mercaptobenzothiazolyl (Z)‐2‐(2‐amino‐4‐thiazolyl)‐2‐acetoxyiminoacetate 4 was affected by using triphenylphosphine and triethylamine, and acylation of 7‐amino‐3‐vinylcephem‐4‐carboxylic acid 5 followed by deprotection with K₂CO₃ in the presence of ammonium chloride in the same pot yielded crude Cefdinir. Purification of crude Cefdinir through resin and treatment of the resulting wet product with trifluoroacetic acid gave highly pure TFA salt of Cefdinir 6, which on neutralization afforded 1a in excellent yield. The impurity profiling of this compound has also been discussed.

Keywords:

• antibacterial drug
• Cefdinir
• impurities
• synthesis

Acknowledgment

The authors thank the management of Aurobindo Pharma Ltd., Research and Development Department, for supporting this work. The authors also thank the Analytical Research Department for their valuable contribution to this work.