d-萘普生中间体2-(6’-甲氧基-2’-萘基)丙烯酸合成方法的研究

Study on the Synthetic Method of d-Naproxen's Intermediate 2-(6'-methoxy-2'-naphthyl) Propenoic Acid

以丙酮酸乙酯 (Ⅱ )和 2 萘甲醚 (Ⅰ )为原料 ,在AlCl3 催化下反应合成了 2 羟基 2 (6’ 甲氧基 2’ 萘基 )丙酸乙酯 (Ⅲ )。最佳反应条件为 :n(Ⅱ )∶n(Ⅰ ) =1 2∶1 ,反应温度为 0～ 5℃ ,反应时间为 1 5h。Ⅲ经碱催化水解 32h得 2 羟基 2 (6’ 甲氧基 2’ 萘基 )丙酸 (Ⅳ ) ,此两步反应收率为 74 8%。Ⅳ经酸催化脱水得 2 (6’ 甲氧基 2’ 萘基 )丙烯酸 (Ⅴ ) ,收率为 84.6 %。Ⅴ经立体加氢即得d 萘普生 (Ⅵ )。

Ethyl [2 hydroxy 2 (6' methoxy 2' naphthyl)] propionate (Ⅲ) was synthesized by the reaction of ethyl pyruvate (Ⅱ) and 2 methoxynaphthalene (Ⅰ) in the presence of the catalyst AlCl\-3.The optimum reaction conditions were:mole ratio of Ⅱ∶Ⅰ=1 2∶1,reaction temperature 0-5 ℃ and reaction time 1 5 h.Ⅲ was hydrolyzed in the presence of alkali for 32 h to give 2 hydroxy 2 (6' methoxy 2' naphthyl) propionic acid (Ⅳ).The yield of above two reactions was 74 8%.Ⅳ was dehydrated in the presence of acid to give 84.6% 2 (6' methoxy 2' naphthyl) propenoic acid (Ⅴ).Ⅴ was asymmetrically hydrogenated to prepare d naproxen (Ⅵ).