5-Methoxytetralone → HCID 10264769, compound

Participants

Reaction Steps

Neo-tanshinlactone (1) was synthesized by a 8-step sequence, as illustrated in Scheme 1. Our synthetic strategy was to first prepare 8-methyl-1-naphthol (6). Accordingly, 5-methoxy-1-tetralone (2) was reacted with methylmagnesium bromide, and without purification, the resulting crude product (3) was dehydrated using concentrated HCl (Y.-G. Suh et al., Chem. Commun., 1203-1204 (2000); P. Mayer et al., Heterocycles, 55(2), 387-392 (2000)). The product 4, after purification, was dehydrogenated over 10% Pd/C in refluxing triglyme to furnish compound 5. Demethylation of 5 with BBr3 gave the desired naphthol intermediate 6 after silica gel chromatography. The total yield over for the four steps (2→6) was 70%. Treatment of 6 with malonic acid in the presence of PPA at 75° C. yielded 7 (H. Kamijo et al., Nippon Kagaku Kaishi, 11, 1257-1262 (1993)). Reaction of 7 with chloroacetone under basic conditions in DMF, followed by reaction with PPA at 110° C. gave the target product 1. (Y.-L. Chen et al., Helvetica Chimica Acta, 79, 651-657 (1996) B. Rajitha et al., Indian J. Chem., 25B, 872-873 (1986))

Provenance & Evidence