Study On Synthesis Of Tamsulosin Hydrochloride

Tamsulosin hydrochloride, with its chemical name is (R)-5-[2-[[2-(ethoxyphenoxy)ethyl]amino]propyl]-2-methoxybenzenesulfona-mide hydrochloride, belongs to a kind of a block agent, can be used in treatment of benign prostatic hyperplasia(BPH). Tamsulosin selectively antagonizes the alA adrenoceptor, previously designted the cloned α1D adrenoceptor. It could bring down the tension of unstriated muscle, improve the symptom of dysuresia, its applied prospect was recognized widely.In this paper, the synthesis of Tamsulosin hydrochloride from p-methoxyphenyl acetone was briefly reviewed. The starting material was chlorosulfonated with chlorosulfonic acid to give2-methoxy-5-(2-oxopropyl)benzenesulfochloride(2).2was aminolyzed by ammonia to get2-methoxy-5-(2-oxopropyl)benzenesulfonamide(3).3was reductive aminated with R-a-phenylethylamine to obtain (R,R)-2-methoxy-5-[2-(methylbenzylamino)propy1]benzenesulfonamide hydrochloride(4).4was missed of the benzyl group to get (R)-(-)-5-(2-aminopropyl)-2-methoxybenzenesulfonamide hydrochloride(5).5was alkylated with1-(2-bromoethoxy)-2-ethoxy benzene, the salt was formated to get Tamsulosin hydrochloride(1), the overall yield of the reactions is21.1%.Secondly, a new alkylation reagent was prepared with o-ethoxyphenol as the starting material. The phenol first condensed with ethylene carbonate, and then reacted with p-toluene sulfonyl chloride to get2-tosyloxyethyl-o-ethoxyphenyl ether.Thirdly, the resolution of racemic Tamsulosin with s-(+)-camphor-10-sulfonic acid was executed, gained some R-Tamsulosin with low optical purity.At last, most of the products were characterized by elemental analysis, IR,1H-NMR,13C-NMR.