A New Synthesis of 8-Methoxypsoralene
Brautigan, David L.
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The present work was undertaken to develop a high-yield synthesis of 8-methoxypsoralene. The synthesis begins with pyrogallol (XIII), which is methylated with dimethyl sultate to form 1,2,3-trimethoxy- benzene (XIV). This is brominated to form 1,5-dibromo-2, 3,4-trimethoxybenzene (XV), which is converted to 5-bromo-2,3,4-trimethoxybenzaldehyde (XVI) with n-butyllithium and dimethylformamide. The methoxy group ortho to the formyl group is then cleaved with boron trichloride, forming 5-bromo-3,4-dimethoxysalicylaldehyde (XVII). Treatment with methyl bromoacetate and potassium carbonate gives methyl (4'-bromo- 2',3'-dimethoxy-6'.tormylphenoxy)acetate (XVIII) which is hydrolyzed with base to give 4'-bromo-2',3'-dimethoxy-6'.formylphenoxyacetic acid (XIX). Cyclization to 5-bromo-6,7-dimethoxybenzofUran (XX) is done with acetic anhydride, acetic acid, and sodium acetate. Treatment with n-butyllithium and dimetbylformam1de gives 6.7-dimethoxy-5-to~1- QenzoiUran (XXI), and cleavage with boron trichloride gives 5-tormyl- 6-byd~XY-7-methoxybenzo£Uran (XXII). The final cyclization to 8-methoxypsoralene (XXIII) is an iodine catalyzed Perkin condensation.