Phloroglucinol → 5,7-Dihydroxy-8-propionyl-4-propyl-2H-chromen-2-one

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Reaction Steps

The key intermediate in the inventive method of preparation is chromene 4, which is synthesized by the sequence depicted in Scheme I. Thus, 5,7-dihydroxy-4-propylcoumafin, 2,5 was prepared quantitatively from ethyl butyrylacetate and phloroglucinol under Pechman conditions.6Product yield and purity was dependent on the amount of sulfuric acid used. The 8-position of 5,7-dihydroxy-4-propylcoumafin, 2, was then selectively acylated at 8°-10° C. by propionyl chloride and A1Cl3 in a mixture of carbon disulfide and nitrobenzene to afford 5,7-dihydroxy-8-propionyl-4-propylcoumarin, 3. A route developed for synthesis of Mammea coumarins7 was initially attempted for preparation of compound 3, but it proved too awkward and low-yielding. The chromene ring was introduced upon treatment of compound 3 with 4,4-dimethoxy-2-methylbutan-2-ol,8 providing 4 in 78% yield. ##STR2##

Provenance & Evidence