Cefdinir synthesis

Yield:91832-40-5 85.8%

Reaction Conditions:

Stage #1:(6R,7R)-7-amino-3-vinyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid;S-(2-benzothiazolyl) 2-(2-aminothiazol-4-yl)-2(Z)-trityloxyiminothioacetate with triethylamine in N,N-dimethyl acetamide at 15 - 20; for 4 h;
Stage #2: with hydrogenchloride;methoxybenzene in dichloromethane;N,N-dimethyl acetamide at -15 - -10; for 2 h;

Steps:

1 Example 1
In a dry reaction flask, add 30g 7-AVCA, 85g cefdinir side chain active ester and 100 ml dimethylacetamide. Control temperature at 15 °C -20 °C. Add dropwise 30g triethylamine. Stir the reaction for 4h. The reaction completely becomes clear. After the reaction is complete, add 250 ml dichloromethane. Lower the temperature to -15 °C - -10 °C. Add 50 ml anisole. Place dry hydrogen chloride gas. After about 2h, HPLC measured end point of the reaction, the reaction after the end of the, through N₂Away excess hydrogen chloride gas in the system. Then add 100 ml H₂O, dropping 10% of Na₂CO₃Solution, adjusting the pH value of 5.5 - 6.0, the temperature does not exceed 5 °C, layered. The aqueous phase is then added to 100 ml CH₂Cl₂Extraction, layered, add aqueous 3g decolorized with active carbon, the decolorization 1h after filtering, adding 500 ml water, for 2 mol/L hydrochloric acid to adjust the pH value to 2.2 - 2.4, temperature control 20 °C -25 °C, nourishing crystal 2h after filtering, washing, alcohol washing, drying, to obtain cefdinir 45g, yield 85.8%, the purity is ≥ 99%.

References:

China Union Chempharma (Suzhou) Co., Ltd.;Suzhou No.3 Pharmaceutical Factory Co., Ltd.;Zhou, Zijin;Zhang, Bo;Huang, Junhao;Chen, Feng;Luo, Xinzu;Yang, Long;Hu, Liyong;Wang, Lei CN106279207, 2017, A Location in patent:Paragraph 0030; 0031; 0032

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