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【结 构 式】 
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【分子编号】22441 【品名】(S)-(4-chlorophenyl)(2-pyridinyl)methyl 4-piperidinyl ether 【CA登记号】 |
【 分 子 式 】C17H19ClN2O 【 分 子 量 】302.80344 【元素组成】C 67.43% H 6.32% Cl 11.71% N 9.25% O 5.28% |
合成路线1
该中间体在本合成路线中的序号：(II)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.
| 【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 |