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目的研究青光眼治疗药盐酸左布诺洛尔的合成工艺。方法以1,5-萘二磺酸钠为原料经碱熔法制得1,5-萘二酚,经雷尼镍催化氢化得到5-羟基萘满酮,用环氧氯丙烷醚化,不经分离直接用叔丁胺氨化,最后用右旋酒石酸拆分消旋体得到盐酸左布诺洛尔。结果与结论目标化合物的结构经比旋光度、IR和1H-NMR谱确证。消旋体收率达79%(以5-羟基萘满酮计),拆分率达32%(以消旋体计),光学纯度(ee值)为100%,达到美国药典标准。该合成路线操作简便,成本降低,适合工业化生产。
Objective To study the synthesis of levobunolol hydrochloride, a therapeutic agent for glaucoma. Methods 1,5-naphthalenediol was obtained from sodium 1,5-naphthalenedisulfonate by alkali fusion method. The 5-hydroxynaphthacene was obtained by catalytic hydrogenation with Raney nickel and etherified with epichlorohydrin Isolation directly with tert-butylamine ammoniation, and finally with dextrose tartaric acid racemate to give the left-class norolol hydrochloride. Results and Conclusions The structures of the target compounds were confirmed by specific rotation, IR and 1H-NMR spectra. The racemate yield was 79% (based on 5-hydroxynaphthamodone), resolution was 32% (as racemate) and optical purity (ee value) was 100%, reaching the US Pharmacopoeia standard. The synthesis route easy to operate, lower costs, suitable for industrial production.