Dimethyl Carbonate → HCID 23045033, compound

Participants

Reaction Steps

A mixture of 7,8-dimethyl-3,4-dihydro-1-benzoxepin5(2H)-one (1.3 g), sodium methoxide (2.0 g) and dimethyl carbonate (30 ml) is heated under reflux for 6 hours with stirring. The reaction mixture is treated in a manner as in Reference Example 11 to give methyl 7,8-dimethyl-5-oxo-2,3,4,5-tetrahydro-1-benzoxepin-4-carboxylate as a colorless oily product (1.3 g). This product (1.2 g) is dissolved in a mixture of methylene chloride (40 ml) and methanol (50 ml). To the solution is added sodium borohydride (0.3 g) in limited amounts, and the mixture is stirred. After addition of water, the reaction mixture is extracted with methylene chloride. The organic layers are combined, washed with water, dried, and concentrated under reduced pressure. To the residue are added methanol (2 ml) and a 1N aqueous solution of sodium hydroxide (10 ml). The mixture is stirred at 60° C. for 15 minutes. To the reaction mixture are added water and ether and the mixture is shaken. Then the aqueous layer is separated. The aqueous layer is acidified with dilute hydrochloric acid, followed by extraction with methylene chloride. The organic layers are combined, washed with water, dried, and concentrated under reduced pressure. To the residue are added dioxane (8 ml) and concentrated hydrochloric acid (1 ml). The mixture is stirred at 100° C. for 40 minutes. To the reaction mixture is added water, followed by extraction with ethyl acetate. The organic layer is washed with water, dried, and evaporated to dryness. The residue is recrystallized from ethyl acetate to afford 7,8-dimethyl-2,3-dihydro-1-benzoxepin-4-carboxylic acid as colorless needles (0.75 g), m.p. 266°-267° C.

Provenance & Evidence