Synthesis Of Celiprolol Hydrochloride

( )-N-[3-Acetyl-4-[(1,1-dimethylethyI)amino]-2-hydroxypropoxy]phenyl]-N,N-die thlurea monhydrochloilde(Celiprolol Hydrochloride) is a favorable medicine in treatment of angina pectoris and hypertension.It is reported in literature [14] that Celiprolol Hydrochloride is prepared by substitution of 4-nitrophenetole, acidylation of amine, Friedel-Crafts reaction, Williamson A.W. synthesis of ether, followed opening of ring and salt forming. The yield of every process respectively is 91.6%, 89%, 85%, 70%, and 74%. The gross yield is 35.9%.It is reported in literature [3] that Celiprolol Hydrochloride is prepared by substitution of 4-chloronitrobenzene, etherification, reduction of nitro group, acidylation of amine, Friedel-Crafts reaction, Williamson A.W. synthesis of ether, followed opening of ring and salt forming. The yield of every process respectively is 90%, 95%, 91.6%, 93.4%, 71.3%, 71.2%, and 80.1%. The gross yield is 29.7%.A commercial and practical synthesis way with 4-chloronitrobenzene as start material is chosen. Celiprolol Hydrochloride is prepared by substitution of 4-chloronitrobenzene, esterification, reduction of nitro group, acidylation of amine, Fries rearrangement of aromatic compounds, Williamson A.W. synthesis of ether, followed opening of ring and salt forming. The yield of every process respectively is 90%, 92%, 90%, 85%, 76%, and 81.3%. The gross yield is 39.1%.A lot of experiments and some improvements are made. During the synthesis of O-AC-4-nitrophenol catalytic hydrogenation replace deoxidization by Na2S. In the study of synthesizing 3-(3-acyl-4-hydroxybenzyl)-l, 1-bisethylurea melt of material NaCl and AlCl3 substitutes nitro phenyl, which is toxic and pollutes the environment.By comparison with the original material, many improvements are made on technology, production cost, reduced pollution, and operation so on.