Dicyclohexylcarbodiimide → N,N'-Dicyclohexylurea

HRID 461776Notes

Reaction equation

HRID 461776 reaction equation
[OH:1]N1C(=O)CCC1=O.[CH:9]1([N:15]=[C:16]=[N:17][CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1>O1CCCC1>[CH:18]1([NH:17][C:16]([NH:15][CH:9]2[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14]2)=[O:1])[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1

Participants

4

Reactant 2

HCID 10868DicyclohexylcarbodiimideHCID 80170N-Hydroxysuccinimide2×

Product 1

HCID 4277N,N'-Dicyclohexylurea

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The half-ester of the formula (V) may be converted into an "activated" ester prior to reaction with the 7-(α-aminoaryl-acetamido)-Δ3 -cephem derivative, using the preferred reagent N-hydroxy-succinimide in the presence of a dehydrating agent such as dicyclohexylcarbodiimide. The "activated" ester product of the formula: ##STR10## is then conveniently reacted wiht the Δ33 -cephem derivative in the reaction solution in which it is formed, without any prior isolation being necessary. In a typical pocedure, a solution of the half-ester, N-hydroxy-succinimide and a 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 is removed, preferably by means of filtration. To the solution containing the "activated" ester, there is then added a solution of the Δ3 -cephem derivative, and the reaction equilibrium generally shifts substantially to completion in the presence of a tertiary amine or inorganic base, as hereinbefore exemplified and preferably with stirring during a period from about one to about 12 hours at room temperature. The solvent may then be removed, e.g., by means of evaporation in vacuo, and the residue dissolved in water, with the aqueous solution then being acidified to a low pH value and subsequently extracted with a water-immiscible organic solvent, e.g., ethyl acetate. The resultant organic phase is then subjected to a procedure similar to that described in method (1) for the isolation and purification of the product.

Workup

  1. customis formed

Sources & evidence

ORD record
ord-04ba201bfe72463187fcb6e169977850
Source dataset
uspto-grants-1977_12
Patent number
US04064241

Reaction notes

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