p-Toluenesulfonic acid monohydrate → 7-(Imidazol-2-yl)amino-3-(1,3,4-thiadiazol-2-yl)thiomethylceph-3-em-4-carboxylic acid

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Reaction Steps

To a solution of toluene-p-sulphonic acid hydrate (54 mg.) in dry DMF (1 ml.) was added 2-fluoro-1-triphenylmethylimidazole (110 mg.) and the solution heated in a preheated bath at 80°. After 5 minutes, to allow complete formation in situ of 2-fluoroimidazole, 7-amino-3-(1,3,4-thiadiazol-2-yl)thiomethylceph-3-em-4-carboxylic acid (110 mg.) was added and heating continued for 2.5 hours. A further portion of the fluoroimidazole (50 mg.) was then added, heating was continued for a further 30 minutes, and the mixture was cooled and evaporated at room temperature. To the residue was added water (10 ml.) and ethyl acetate (25 ml.) and the mixture filtered and the phases separated. The aqueous layer was concentrated to 4 ml., filtered and subjected to preparative HPLC on Whatman "Partisil 10" using water/MeOH/HOAc 80:20:1 v/v/v as eluant. The product crystallised on addition of acetone. It was washed with acetone and ether to give 7-(imidazol-2-yl)amino-3-(1,3,4-thiadiazol-2-yl)thiomethylceph-3-em-4-carboxylic acid (15 mg.) having the following n.m.r. in d6DMSO+CD3COOD: 3.52 (d, 1H); 3.79 (d, 1H); 4.33 (d, 1H); 4.6 (d, 1H); 5.12 (d, 1H); 5.58 (d, 1H); 6.83 (s, 2H); 9.49 (s, 1H).

Provenance & Evidence