Water → HCID 19841173, compound

Participants

Reaction Steps

6,7-Dimethoxy-1-oxo-1,2,3,4-tetrahydro-2-naphthoic acid methyl ester [Hashem et al., J. Med. Chem., 19, 229 (1976)] (14 g) is dissolved in a mixture of methylene chloride (200 ml) and methanol (200 ml). Sodium borohydride (1 g) is added to the solution with stirring at room temperature, and the mixture is then stirred for one hour. The resulting mixture is supplemented with sodium borohydride (1 g) and the mixture is stirred for 30 minutes. To the resultant is then further added sodium borohydride (0.5 g) and the mixture is stirred for 30 minutes. After addition of water (500 ml) to the mixture, the methylene chloride layer is separated. The aqueous layer is extracted with methylene chloride (200 ml). The extracts are combined and concentrated under reduced pressure to give the methyl ester of 6,7-dimethoxy-1-hydroxy-1,2,3,4-tetrahydro-2-naphthoic acid. This product is dissolved in methanol (10 ml), and an aqueous solution (100 ml) of sodium hydroxide (14 g) is added dropwise to the solution at room temperature with stirring. After finishing the dropwise addition, the mixture is allowed to stand at room temperature for 30 minutes. Water (200 ml) is added to the mixture, and the mixture is extracted with a mixture of ethyl ether (100 ml) and petroleum ether (100 ml). The aqueous layer is made acid with concentrated hydrochloric acid and extracted with methylene chloride (300 ml). The extract is washed with water, dried and concentrated under reduced pressure. To the residue are added dioxane (100 ml) and concentrated hydrochloric acid (10 ml), and the mixture is heated at 80° C. for 5 minutes. The reaction mixture is concentrated under reduced pressure to half of its original volume. To the concentrate is added an aqueous solution (200 ml) of sodium hydroxide (10 g). The mixture is extracted with a mixture of ether (50 ml) and petroleum (50 ml). The aqueous layer is made acid with concentrated hydrochloric acid, and then precipitating colorless prisms are collected by filtration to give 1,2-dihydro-6,7-dimethoxy-3-naphthoic acid (6.2 g), m.p. 191°-194° C.

Provenance & Evidence