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【结 构 式】 
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【分子编号】30368 【品名】(3S,4R)-4-(3-methoxyphenyl)-1,3-dimethyl-4-propylpiperidine; 3-[(3S,4R)-1,3-dimethyl-4-propylpiperidinyl]phenyl methyl ether 【CA登记号】 |
【 分 子 式 】C17H27NO 【 分 子 量 】261.40752 【元素组成】C 78.11% H 10.41% N 5.36% O 6.12% |
合成路线1
该中间体在本合成路线中的序号：(VI)The methylation of 2-methyl-3-propyl-3-(3-methoxyphenyl)-1-pyrroline (I) with dimethyl sulfate in refluxing butanone gives 1-methyl-3-propyl-2-exo-methylene-3-(3-methoxyphenyl)pyrrolidine (II), which by reaction with HBF4 in ethanol is converted into 1,2-dimethyl-3-propyl-3-(3-methoxyphenyl)pyrrolinium tetrafluoroborate (III). The methylation of (III) with diazomethane in dichloromethane ether yields 1,2-dimethyl-3-propyl-3-(3-methoxyphenyl)-1,2-ethylenepyrrolidinium tetrafluoroborate (IV), which by heating at 180 C and neutralization with NaOH affords 1,3-dimethyl-4-propyl-4-(3-methoxyphenyl)-1,4,5,6-tetrahydropyridine (V). The reduction of (V) with NaBH4 in THF gives 1,3-dimethyl-4-propyl-4-(3-methoxyphenyl)piperidine (VI), which is finally treated with 48% HBr in refluxing acetic acid.
| 【1】 Zimmerman, D.M. (Eli Lilly and Company); 1,3,4-Trisubstituted-4-arylpiperidines and their preparation. BE 0833044; DE 2539452; FR 2283679; FR 2299337; GB 1525584; JP 7648670; JP 7783572 . |
| 【2】 Castaner, J.; Serradell, M.N.; Picedanol Hydrochloride. Drugs Fut 1984, 9, 3, 204. |
| 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) | 30363 | 4-(3-methoxyphenyl)-5-methyl-4-propyl-3,4-dihydro-2H-pyrrole; methyl 3-(5-methyl-4-propyl-3,4-dihydro-2H-pyrrol-4-yl)phenyl ether | C15H21NO | 详情 | 详情 | |
| (II) | 30364 | methyl 3-(1-methyl-2-methylene-3-propyl-3-pyrrolidinyl)phenyl ether; 3-(3-methoxyphenyl)-1-methyl-2-methylene-3-propylpyrrolidine | C16H23NO | 详情 | 详情 | |
| (III) | 30365 | 4-(3-Methoxyphenyl)-1,5-dimethyl-4-propyl-3,4-dihydro-2H-pyrrolium tetraflluoroborate | C16H24BF4NO | 详情 | 详情 | |
| (IV) | 30366 | 4-(3-Methoxyphenyl)-1,5-dimethyl-4-propyl-1-azoniabicyclo[3,1,0]hexane tetrafluoroborate | C17H26BF4NO | 详情 | 详情 | |
| (V) | 30367 | 4-(3-methoxyphenyl)-1,5-dimethyl-4-propyl-1,2,3,4-tetrahydropyridine; 3-(1,5-dimethyl-4-propyl-1,2,3,4-tetrahydro-4-pyridinyl)phenyl methyl ether | C17H25NO | 详情 | 详情 | |
| (VI) | 30368 | (3S,4R)-4-(3-methoxyphenyl)-1,3-dimethyl-4-propylpiperidine; 3-[(3S,4R)-1,3-dimethyl-4-propylpiperidinyl]phenyl methyl ether | C17H27NO | 详情 | 详情 |