Bepotastine besilate, Betotastine besilate, TAU-284DS, TAU-284, Talion
苯磺酸贝托司汀 贝他斯汀 贝托斯汀Chemical Name: (+)-(S)-4-[4-[1-(4-Chlorophenyl)-1-(2-pyridyl)methoxy]piperidin-1-yl]butyric acid monobenzenesulfonate; (+)-(S)-4-[4-[(4-Chlorophenyl)(2-pyridyl)methoxy]piperidin-1-yl]butyric acid monobenzenesulfonate
CAS No. 190786-44-8, 190786-43-7 (free base), 125602-71-3 (free base undefined isomer)
项目整合开发状态: Launched-2000
项目研究机构: Ube (Originator), Senju (Licensee), Tanabe Seiyaku (Licensee)
合成路线:The reaction of 4-[1-(4-chlorophenyl)-1-(2-pyridyl)methoxy]piperidine (I) with ethyl 4-bromobutyrate (II) by means of K2CO3 in refluxing acetone gives the corresponding condensation product (III),which is then hydrolyzed with NaOH in ethanol/water yielding compound (IV).
📌 参考资料/链接：
参考文献标题:Piperidine and piperazine derivs.,process for preparing the same and pharmaceutical compsns.containing them
文献作者:Koda,A.; Kuroki,Y.; Fujiwara,H.; Takamura,S.; Yamano,K.(Ube Industries,Ltd.)
参考来源:EP 0335586; JP 1989242574; JP 1990025465; JP 1993294929; US 4929618
📄 详细内容
合成路线:A new synthesis of betotastine has been developed: The racemic 4-[1-(4-chlorophenyl)-1-(2-pyridyl)methoxy]piperidine (I) is submitted to optical resolution with N-acyl amino acids such as N-acetyl-L-phenylalanine (preferred),N-acetyl-L-leucine,N-(benzyloxycarbonyl)-L-phenylalanine,N-(benzyloxycarbonyl)-L-valine,N-(benzyloxycarbonyl)-L-threonine,N-(benzyloxycarbonyl)-L-serine or with (2R,3R)-3-(5-chloro-2-nitrophenylsulfanyl)-2-hydroxy-3-(4-methoxyphenyl)propionic acid (preferred) or (2R,3R)-2-hydroxy-3-(4-methoxyphenyl)-3-(2-nitrophenylsulfanyl)propionic acid as chiral intermediates,yielding the (S)-isomer (II).The condensation of (II) with ethyl 4-bromobutyrate (III) by means of a base such as Na2CO3,NaHCO3,K2CO3 or KHCO3 gives the expected 4-(1-piperidinyl)butyric acid ester (IV),which is finally hydrolyzed with NaOH or KOH in aqueous ethanol or methanol.
参考文献标题:Acid-addition salts of optically active piperidine cpd.and process for producing the same
文献作者:Kita,J.; Yoshioka,R.; Ozaki,Y.; Takemura,S.; Fujiwara,H.; Yamada,S.(Tanabe Seiyaku Co.,Ltd.; Ube Industries,Ltd.)
参考来源:JP 1998237070; JP 2000198784; WO 9829409
合成路线:The reaction of 4-[1-(4-chlorophenyl)-1-(2-pyridyl)methoxy]piperidine (I) with ethyl 4-bromobutyrate (II) by means of K2CO3 in refluxing acetone gives the corresponding condensation product (III),which is then hydrolyzed with NaOH in ethanol/water yielding compound (IV).
参考文献标题:Betotastine besilate
文献作者:Castar,J.; Graul,A.
参考来源:Drugs Fut 1998,23(3),256