Methanol → (6R,7R)-7-amino-3-(1-methyl-1-pyrrolidinio)methylceph-3-em-4-carboxylate monohydroiodide

Participants

Reaction Steps

To the filtrate containing the trimethylsilyl 7-(trimethylsilyl)amino-3-iodomethylceph-3-em-4-carboxylate at 0°-5° C. under an inert atmosphere of dry nitrogen was added 3.82 ml (36.7 mmoles, 1.0 equivalent) of 97% N-methylpyrrolidine (dried over molecular sieves) dropwise by syringe at such a rate so as to maintain a reaction temperature of less than 10° C. The resulting slurry was stirred an additional 15 minutes at 0°-5° C. After this time. 5.0 ml (123 mmoles, 3.35 equivalent) of methanol was added dropwise while maintaining a reaction temperature of less than 10° C. The resulting thin slurry was stirred an additional 15 minutes at 0°-5° C. The solid was suction filtered, washed with Freon TF (1×100 ml) and partially dried under suction for 15 minutes. Further drying in vacuo at ambient temperature to constant weight afforded 10.27 g (66%) of (6R,7R)-7-amino-3-(1-methyl-1-pyrrolidinio)methylceph-3-em-4-carboxylate monohydroiodide. The 360 MHz 1H NMR spectrum of this crude material (D2O) showed a Δ3 /Δ2 isomer ratio of 5.4/1; the HPLC chromatogram of the salt showed a Δ3 /Δ2 area % ratio of 8.1/1. The activity yield for the conversion of 7-ACA to 7-amino-3-(1-methyl-1-pyrrolidinio)methylceph-3-em-4-carboxylate was 43.5% (determined by HPLC quantitation of the salt versus a reference standard of the desired Δ3 isomer).

Provenance & Evidence