Coumarins via the wittig reaction. Synthesis of methoxsalen‐5‐¹⁴C

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 14C 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.

Combinatorial discovery of two-photon photoremovable protecting groups

“…3). This known compound (50,51) was alkylated with nitrobenzylbromide͞KF͞alumina. Irradiation of 13 (Rayonet photochemical reactor, 350 nm) produces coumarin in quantitative yield.…”

Anti-Alzheimer potential of coumarin derivatives: A review

“…Coumarins can be synthesized by various reactions such as Pechmann condensation reaction [45], Knoevenagel condensation reaction [48], Perkin reaction [49], Wittig reaction [50], Claisen condensation reaction [51]. Among all these reactions Pechmann reaction are the mostly used reaction which involves the simple starting materials like phenols and β-ketoesters in the presence of acidic condensing agents to produce coumarins.…”

Benzopyrone, a privileged scaffold in drug discovery: An overview of FDA‐approved drugs and clinical candidates

“…A subsequent reaction of 56 with dimethyl sulfate followed by treatment with sublimed sulfur and dehydrogenation produces methoxsalen 18 (Figure 14). 191 Oda et al reported the total synthesis of bergapten (19) in a nine-step reaction series. The treatment of phloroglucinol 58 with methanol at 70°C in dioxane in a sealed tube produces monomethyl derivative 59 (89% yield).…”