Synthesis
General procedure for the synthesis of (6R,7R)-7-amino-3-(hydroxymethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid from 7-aminocephalosporanic acid (7-ACA): 27.2 g (0.1 mol) of 7-ACA were accurately weighed and placed in a reaction flask, to which 50 mL of methanol and 50 mL of water were added as solvents. 3.0 g of tetra-n-butyl ammonium chloride was added while stirring at a temperature of -5 to 5 °C. Subsequently, 2 mol/L sodium hydroxide solution was added slowly dropwise. After the dropwise addition was completed, the reaction temperature was maintained and stirring was continued for 0.5 to 1 hour. Upon completion of the reaction, the pH of the reaction solution was adjusted to neutral with 30% hydrochloric acid, at which point a solid precipitated. The solid product was collected by diafiltration and washed with anhydrous ethanol. Eventually, 20.7 g of dry white solid product was obtained. The product was analyzed by high performance liquid chromatography (HPLC) and the purity of the product was 97.35% (area normalization method) and the content of lactone impurities was 0.33%.
References
[1] Patent: CN105131017, 2017, B. Location in patent: Paragraph 0041-0042
[2] Synthetic Communications, 2003, vol. 33, # 14, p. 2475 - 2482
[3] Patent: CN106083894, 2016, A. Location in patent: Paragraph 0045; 0054; 0055; 0056; 0057
[4] Synthesis, 2012, vol. 2012, # 2, p. 207 - 214
[5] Farmaco, 2003, vol. 58, # 6, p. 409 - 418
