Triethylamine → 6-(3-[Carbamoyl]-acrylamido)-2,2-dimethyl-3-(5-tetrazolyl)penam

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Reaction Steps

To a stirred mixture of 1.15 g. (10 m mole) of maleamic acid and 1.40 ml. of triethylamine in 40 ml. of dry tetrahydrofuran, at 0° C., is added 1.57 ml (12 m mole) of isobutyl chloroformate followed by three drops of N-methylmorpholine. Stirring is continued for a further 30 minutes at 0° C. To this mixed anhydride is then added a solution prepared by adding 2.40 g. (10 m mole) of 6-amino-2,2-dimethyl-3-(5-tetrazolyl)penam to a mixture of 15 ml. of water and 15 ml. of tetrahydrofuran and adjusting the pH to 7.5. The resulting mixture is then stirred for a further 1 hour at 0° C. At this point, the tetrahydrofuran is removed by evaporation in vacuo, and the residue is diluted with more water. The pH is adjusted to 8.0 with 6 N sodium hydroxide, and then the mixture is extracted with ethyl acetate. The extracts are discarded. The pH of the residual aqueous phase is adjusted to 2.0 with 4 N hydrochloric acid and then the product is extracted into ethyl acetate. The organic layer is dried and concentrated in vacuo to give 6-(3-[carbamoyl]acrylamido)-2,2-dimethyl-3-(5-tetrazolyl)penam (1.03 g., 33% yield). The infrared spectrum (KBr disc) of the product shows absorption band at 1818 cm-1 (β-lactam) and 1692 cm-1. The NMR spectrum (DMSO-d6) shows bands at 7.00 and 6.25 (quartet, 2H, J=12 Hz, olefinic hydrogens), 5.80-5.48 ppm (multiplet, 2H, C-5 and C-6 hydrogens), 5.26 ppm (singlet, 1H, C-3 hydrogen), 1.65 ppm (singlet, 3H, C-2 methyl hydrogens) and 1.06 ppm (singlet, 3H, C-2 methyl hydrogens).

Provenance & Evidence