2,2,2-Trifluoroethyl Chlorooxoacetate—Universal Reagent for One-Pot Parallel Synthesis of N¹-Aryl-N²-alkyl-Substituted Oxamides

Abstract

A one-pot parallel synthesis of N(1)-aryl-N(2)-alkyl-substituted oxamides with 2,2,2-trifluoroethyl chlorooxoacetate was developed. The synthesis of a library of 45 oxamides revealed higher efficiency of this reagent over the known ethyl chlorooxoacetate. The reagent was successfully used to prepare the known oxamide-containing HIV entry inhibitors.

Facile One-Pot Parallel Synthesis of 3-Amino-1,2,4-triazoles

“…The latter compound is a stable yet reactive thiocarbonate ester; it is readily accessible in one step from thiophosgene and trifluoroethanol via fractional distillation (Scheme ). Based on our previous findings, the usage of the trifluoroethyl substituents as leaving groups enables to achieve suitable profiles of kinetics and selectivity of the stepwise aminolysis reaction in the case of carbonate esters. , A similar approach applied to thiocarbonate esters gives an excellent starting material for the reliable utilization in synthetic projects, which require the formation of thiocarbamates or thioureas either as target or intermediate compounds. Indeed, compared to volatile and toxic thiophosgene or its analogs, compound 1 is an easy-to-handle reagent that interacts consistently with a wide range of amines.…”

Oxamates as 1,2‐Diketone Equivalents: The Effect of Fluorine

“…Traditionally, oxamates can be generated through the ammonolysis of amines with excess chloro oxoacetates or oxalates. Furthermore, the synthesis of oxamates through an oxidative double cross‐carbonylation of amines and alcohols in the presence of palladium catalyst under low‐pressure CO/O 2 has been well documented [14–16] . A very recent method for primary oxamates uses the oxidative coupling of diazo group containing precursors and NH 4 I [17] .…”

Oxidative Coupling of Diazo and NH4I: A Route to Primary Oxamates and α-Ketoamides

“…These traditional synthetic approaches are based on the acylation of appropriate amines but suffer from the requirement for stoichiometric quantities of monoester oxaloyl chlorides or α-oxoyl chlorides (Scheme 1a). 3 The Pd-catalyzed double carbonylation of the corresponding starting materials with amines also provides an efficient means of generating oxamates and α-ketoamides (Scheme 1b). 4 The disadvantage of the latter strategy is that high-pressure CO is required; at the same time, ethanol is usually used as a solvent for the preparation of oxamates, 4a−c and the range of substrates is narrow.…”