benzhydryl (6R)-3-(iodomethyl)-7-[[(2Z)-2-methoxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate → HCID 178502757, compound

Participants

Reaction Steps

A mixture of diphenylmethyl 7-[(Z)-2-methoxyimino-2-(2-tritylaminothiazol-4-yl)acetamido]-3-iodomethyl-3-cephem-4-carboxylate (VII-1) 468 mg, 0.5 mmole) and 5-(2-t-butoxycarbonylaminoethyl)-4-methylthiazole (242 mg, 1 mmole) [prepared by t-butoxycarbonylation of 5-(2-aminoethyl)-4-methylthiazole; see K. M. Muraveva and M. N. Shchukina, Zh. Obshch. Khim., 33, 3723 (1963); CA, 60, 8012a (1964)] in a mixture of methylene chloride (2 mL) and DMSO (0.5 mL) was stirred for 6 hours at room temperature and diluted with ethyl acetate (100 mL). The mixture was washed with water and evaporated under reduced pressure. The residue was triturated with ether and 400 mg of the quaternary salt was collected by filtration and treated with TFA (5 mL) for 2 hours at room temperature. After removal of TFA under reduced pressure below 20° C., the mixtrue was triturated with ether and 310 mg of the TFA salt of the crude product was collected by filtration. The TFA salt was dissolved in a small amount of aqueous NaHCO3 and chromatographed on a column of HP-20 (1.8×20 cm) by eluting with water. The fractions containing the title compound were combined, concentrated under reduced pressure and freeze-dried to give 36 mg (yield 14%) of the title product [Ij]. Estimated purity 50% (by HPLC).

Provenance & Evidence