Coumarins <i>via</i> the wittig reaction. Synthesis of methoxsalen‐5‐¹⁴C

Abstract

Abstract A new and improved synthesis of methoxsalen ( 3 ) has been developed for the preparation of specifically carbon‐14 labelled 3 . Introduction of the label by a Gattermann reaction on 6‐hydroxy‐7‐methoxycoumaran ( 1 ) followed by dehydrogenation provides an intermediate 6 which, on reaction with carbethoxymethylenetriphenylphosphorane ( 8 ) and heat inversion, provides the title compound in overall yields of up to 50%. By these procedures, 3 has been prepared 14 C labelled at C‐5. Alternatively, 3 may be prepared from 6 and ethyl cyanoacetate in lower overall chemical yield but in potentially higher radiochemical yield if labelling at C‐6 or C‐7 is required since the Wittig process utilizes an excess of phosphorane.