title: B(OCH2CF3)3-mediated direct amidation of pharmaceutically relevant building blocks in cyclopentyl methyl ether.
abstract: The use of B(OCH2CF3)3 for mediating direct amidation reactions of a wide range of pharmaceutically relevant carboxylic acids and amines is described, including numerous heterocycle-containing examples. An initial screen of solvents for the direct amidation reaction suggested that cyclopentyl methyl ether, a solvent with a very good safety profile suitable for use over a wide temperature range, was an excellent replacement for the previously used solvent acetonitrile. Under these conditions amides could be prepared from 18 of the 21 carboxylic acids and 18 of the 21 amines examined. Further optimisation of one of the low yielding amidation reactions (36% yield) via a design of experiments approach enabled an 84% yield of the amide to be obtained.
authors.affiliation: Department of Chemistry, University College London, 20 Gordon St, London, WC1H 0AJ, UK. tom.sheppard@ucl.ac.uk.
authors.forename: Valerija
authors.initials: V
authors.lastname: Karaluka
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Lanigan
authors.forename: Paul M
authors.initials: PM
authors.lastname: Murray
authors.forename: Matthew
authors.initials: M
authors.lastname: Badland
authors.forename: Tom D
authors.initials: TD
authors.lastname: Sheppard
mesh_terms: D000577:Amides / Q000737:chemistry*; D000588:Amines / Q000737:chemistry*; D000631:Aminopyridines / Q000737:chemistry; D001881:Borates / Q000737:chemistry*; D002264:Carboxylic Acids / Q000737:chemistry*; D002384:Catalysis; D003517:Cyclopentanes / Q000737:chemistry*; D004951:Esterification; D008738:Methyl Ethers / Q000737:chemistry*; D010648:Phenylacetates / Q000737:chemistry; D012997:Solvents / Q000737:chemistry
chemical_list: D000577:Amides; D000588:Amines; D000631:Aminopyridines; D001881:Borates; D002264:Carboxylic Acids; D003517:Cyclopentanes; D008738:Methyl Ethers; D010648:Phenylacetates; D012997:Solvents; C025136:phenylacetic acid; C032439:alpha-aminopyridine