Uses
7-Amino-3-(1-methyl-5-tetrazolylthio)methyl-3-cephem-4-carboxylic Acid is a cephalosporin derivative with antibacterial activity. 7-Amino-3-(1-methyl-5-tetrazolylthio)methyl-3-cephem-4-carboxylic Acid
is an intermediate in the preparation of Cefmetazole (C242850) and other semi-synthetic antibiotics.
Synthesis
To a 1000 mL four-neck flask was added 132 mL (141.1 g, 1.57 mol) of dimethyl carbonate and 162 g of boron trifluoride-dimethyl carbonate complex at a controlled temperature of 10-12 °C. Subsequently, 21.5 g (0.185 mol) of 5-mercapto-1-methyltetrazole was added and after stirring for 10 minutes, 50 g (0.184 mol) of 7-aminocephalosporanic acid (7-ACA) was added and the reaction was carried out at 25°C for 45 minutes. After completion of the reaction, the mixture was cooled to 0°C. 32 g (0.283 mol) of chloroacetyl chloride was slowly added dropwise to 37 mL of N,N-dimethylformamide (DMF) solution and the reaction was kept for 45 minutes. To the reaction mixture, 300 mL of water and 300 mL of dimethyl carbonate were added and the phase separation was performed with thorough stirring. The aqueous phase was extracted with 400 mL of dimethyl carbonate and all dimethyl carbonate layers were combined. 5 g of activated carbon was added to decolorize for 30 minutes. Subsequently, the pH was adjusted to 6.8 by dropwise addition of a solution of dimethyl carbonate with triethylamine at 0-5 °C. Crystallization was filtered for 2 h. The filter cake was dried in vacuo at 45 °C to give 67 g (0.180 mol)-7-amino-3-(((1-methyl-1H-tetrazol-5-yl)thio)methyl)-8-oxo-5-thia-1-azabicyclo[4.2.0 ] oct-2-ene-2-carboxylic acid (7-ACT) in 98% yield.
References
[1] Patent: CN105330677, 2016, A. Location in patent: Paragraph 0024
[2] Chemical and Pharmaceutical Bulletin, 1985, vol. 33, # 12, p. 5534 - 5538
[3] Journal of the Iranian Chemical Society, 2016, vol. 13, # 6, p. 1019 - 1025
[4] Patent: CN105585580, 2016, A. Location in patent: Paragraph 0007; 0031; 0032; 0033
[5] Journal of Heterocyclic Chemistry, 1989, vol. 26, # 2, p. 461 - 464
