(RS)-Naproxen methyl ester → 2-(6-Methoxy-2-naphthyl)propionic acid

Participants

Reaction Steps

The oil, 1,1-dimethoxy-1-(6-methoxy-2-naphthyl)-prop-2-yl methanesulfonate, from Example 6 and 4.9 g of sodium acetate is dissolved in 200 ml of glacial acetic acid. The mixture is heated to 90°-100° C. and maintained at that temperature for approximately 3 hours. An additional 3.8 g of sodium acetate is added to the reaction mixture and the mixture is stirred for an additional three hours. The reaction mixture then is heated to 100° C. where it is held for an additional three hours. After that time 200 ml of methylene chloride and 50 ml of water is added to the reaction mixture. The organic and aqeuous layers are separated and the organic layer is evaporated under reduced pressure to afford methyl 2-(6-methoxy-2-naphthyl)propionate. The resulting methyl 2-(6-methoxy-2-naphthyl)propionate is hydrolyzed with a mixture of methanol/potassium hydroxide-water. The reaction mixture is poured into water and extracted with methylene chloride to afford the acid, 2-(6-methoxy-2-naphthyl)propionic acid (melting point: 153°-155° C.).

Provenance & Evidence