Dicyclohexylcarbodiimide → N,N'-Dicyclohexylurea

Participants

Reaction Steps

The half-ester of the formula (VI) may be converted into an "activated" ester prior to reaction with the 7-(α-aminoarylacetamido)-4-carboxy-Δ3 -cephem derivative using the preferred reagent N-hydroxysuccinimide in the presence of a dehydrating agent such as dicyclohexylcarbodiimide. The "activated" ester product of the formula: ##STR5## is conveniently then reacted with the Δ3 -cephem derivative in the reaction solution in which it has been formed, without isolation. In a typical procedure, a solution of the half-ester, N-hydroxysuccinimide and dehydrating agent in a reaction-inert organic solvent, e.g. tetrahydrofuran, is stirred for several hours at room temperature, after which the solid N,N'-dicyclohexylurea formed in the reaction may be removed, e.g. by filtration. To the solution containing the "activated" ester is then added a solution of the Δ3 -cephem derivative, and reaction generally goes substantially to completion in the presence of a tertiary amine or inorganic base, as hereinbefore examplified and preferably with stirring during a period from 1 to 12 hours at room temperature. The solvent may then be removed, e.g. by evaporation in vacuo, and the residue dissolved in water, the aqueous solution then being acidified, extracted with a water-immiscible organic solvent, e.g. ethyl acetate, and the organic phase subjected to a similar procedure to that described in Method (1) for the isolation and purification of the product.

Provenance & Evidence