63740-75-0Relevant articles and documents
Ultrafast chiral separations for high throughput enantiopurity analysis
Barhate, Chandan L.,Joyce, Leo A.,Makarov, Alexey A.,Zawatzky, Kerstin,Bernardoni, Frank,Schafer, Wes A.,Armstrong, Daniel W.,Welch, Christopher J.,Regalado, Erik L.
supporting information, p. 509 - 512 (2017/01/13)
Recent developments in fast chromatographic enantioseparations now make high throughput analysis of enantiopurity on the order of a few seconds achievable. Nevertheless, routine chromatographic determinations of enantiopurity to support stereochemical investigations in pharmaceutical research and development, synthetic chemistry and bioanalysis are still typically performed on the 5-20 min timescale, with many practitioners believing that sub-minute enantioseparations are not representative of the molecules encountered in day to day research. In this study we develop ultrafast chromatographic enantioseparations for a variety of pharmaceutically-related drugs and intermediates, showing that sub-minute resolutions are now possible in the vast majority of cases by both supercritical fluid chromatography (SFC) and reversed phase liquid chromatography (RP-LC). Examples are provided illustrating how such methods can be routinely developed and used for ultrafast high throughput analysis to support enantioselective synthesis investigations.
Analogs of 3-(1-Phenyl-3-oxobutyl)-4-hydroxycoumarin (Warfarin) Prepared from Substituted Salicylic Acids
Obaseki, Andrew O.,Steffen, James E.,Porter, William R.
, p. 529 - 533 (2007/10/02)
Some derivatives of salicylic acid containing substituents meta to the carboxyl group were used to prepare analogs of the anticoagulant drug warfarin, 3-(1-phenyl-3-oxobutyl)-4-hydroxycoumarin, containing substituents in either the 6- or 8-position of the coumarin ring.When the substituent was the hydroxyl group, the resulting products are previously identified metabolites of warfarin.The substituted salicylic acid is first acetylated with acetic anhydride, then either converted to the acid chloride and condensed with diethyl malonate in the presence of sodium hydroxide or converted to the mixed anhydride with formic acid and condensed with ethoxymagnesium diethyl malonate to yield, in either case, the corresponding 3-carbethoxy-4-hydroxycoumarin substituted in the 6- or 8-position of the coumarin ring.These compounds readily condense with benzalacetone to form the corresponding substituted warfarin in the presence of 5 mole percent tertiary amine catalyst.This method offers an improved route for the synthesis or 8-hydroxywarfarin.
