ethyl 4-(4-[[(S)-(4-chlorophenyl)(2-pyridinyl)methyl]oxy]-1-piperidinyl)butanoate -Drug Synthesis Database

【结构式】

【分子编号】22443

【品名】ethyl 4-(4-[[(S)-(4-chlorophenyl)(2-pyridinyl)methyl]oxy]-1-piperidinyl)butanoate

【CA登记号】

【分子式】C₂₃H₂₉ClN₂O₃

【分子量】416.94764

【元素组成】C 66.26% H 7.01% Cl 8.5% N 6.72% O 11.51%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(IV)

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.

参考文献中间体

合成目标

【1】 Kita, J.; Yoshioka, R.; Ozaki, Y.; Takemura, S.; Fujiwara, H.; Yamada, S. (Tanabe Seiyaku Co., Ltd.; Ube Industries, Ltd.); Acid-addition salts of optically active piperidine cpd. and process for producing the same. JP 1998237070; JP 2000198784; WO 9829409 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	16053	2-[(4-chlorophenyl)(4-piperidinyloxy)methyl]pyridine; (4-chlorophenyl)(2-pyridinyl)methyl 4-piperidinyl ether		C₁₇H₁₉ClN₂O	详情	详情
(II)	22441	(S)-(4-chlorophenyl)(2-pyridinyl)methyl 4-piperidinyl ether		C₁₇H₁₉ClN₂O	详情	详情
(III)	11263	ethyl 4-bromobutanoate; Ethyl 4-bromobutyrate	2969-81-5	C₆H₁₁BrO₂	详情	详情
(IV)	22443	ethyl 4-(4-[[(S)-(4-chlorophenyl)(2-pyridinyl)methyl]oxy]-1-piperidinyl)butanoate		C₂₃H₂₉ClN₂O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

参考文献中间体

合成目标

【1】 Zhan ZQ, Zhou ZY, Peng LZ. 2006. Asymmetry synthesis of bepotastine besilate. Zhongguo Yiyao Gongye Zazhi, 37(11): 726～727. Krueger W, Krueger G. 1983. 4-[1-methyl-5-bis[(2-chloroethyl) amino] -2-benzimidazolyl] butyric acid. Ger, (East)DD 159877.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	57809	4-(4-Chlorobenzoyl)pyridine; 4-Chlorophenyl 4-pyridyl ketone	14548-48-2	C₁₂H₈ClNO	详情	详情
(II)	67060	(S)-(4-chlorophenyl)(pyridin-2-yl)methanol		C₁₂H₁₀ClNO	详情	详情
(III)	67061	ethyl 3-(4-bromopiperidin-1-yl)propanoate		C₁₀H₁₈BrNO₂	详情	详情
(IV)	22443	ethyl 4-(4-[[(S)-(4-chlorophenyl)(2-pyridinyl)methyl]oxy]-1-piperidinyl)butanoate		C₂₃H₂₉ClN₂O₃	详情	详情
(V)	67062			C₂₁H₂₅ClN₂O₃	详情	详情

Extended Information