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【结 构 式】 
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【分子编号】37675 【品名】2-(1-piperidinyl)-1-ethanol 【CA登记号】3040-44-6 |
【 分 子 式 】C7H15NO 【 分 子 量 】129.20224 【元素组成】C 65.07% H 11.7% N 10.84% O 12.38% |
合成路线1
该中间体在本合成路线中的序号：(VI)Two related new syntheses of raloxifene have been described: 1) The acylation of N-(6-methoxy-1-benzothiophen-2-yl)-N,N-dimethylamine (I) with 4-fluorobenzoyl chloride (II) by heating at 100 C in chlorobenzene gives the 3-acyl derivative (III), which is condensed with 4-methoxyphenylmagnesium bromide (IV) in THF yielding 3-(4-fluorobenzoyl)-6-methoxy-2-(4-methoxyphenyl)-1-benzothiophene (V). The condensation of (V) with 1-(2-hydroxyethyl)piperidine (VI) by means of NaH in DMF affords the ether (VII), which is finally demethylated with AlCl3 and ethanethiol. 2) The intermediate (III) can also be condensed first with 1-(2-hydroxyethyl)piperidine (VI) by means of NaH as before giving the piperidinoethyl ether (VIII), which is then condensed with the Grignard reagent (IV) affording the previously reported ether (VII).
| 【1】 Bradley, D.A.; et al.; Synergistic methodologies for the synthesis of 3-aroyl-2-arylbenzo[b]thiophene-based selective estrogen receptor modulators. Two concise syntheses of raloxifene. Tetrahedron Lett 1999, 40, 28, 5155. |
| 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) | 30906 | N-(6-methoxy-1-benzothiophen-2-yl)-N,N-dimethylamine; 6-methoxy-N,N-dimethyl-1-benzothiophen-2-amine | C11H13NOS | 详情 | 详情 | |
| (II) | 17263 | 4-fluorobenzoyl chloride | 403-43-0 | C7H4ClFO | 详情 | 详情 |
| (III) | 37673 | [2-(dimethylamino)-6-methoxy-1-benzothiophen-3-yl](4-fluorophenyl)methanone | C18H16FNO2S | 详情 | 详情 | |
| (IV) | 37674 | Bromo(4-methoxyphenyl)magnesium; 4-Methoxyphenylmagnesium bromide | 352-13-6 | C7H7BrMgO | 详情 | 详情 |
| (V) | 21916 | (4-fluorophenyl)[6-methoxy-2-(4-methoxyphenyl)-1-benzothiophen-3-yl]methanone | C23H17FO3S | 详情 | 详情 | |
| (VI) | 37675 | 2-(1-piperidinyl)-1-ethanol | 3040-44-6 | C7H15NO | 详情 | 详情 |
| (VII) | 37677 | [6-methoxy-2-(4-methoxyphenyl)-1-benzothiophen-3-yl][4-[2-(1-piperidinyl)ethoxy]phenyl]methanone | C30H31NO4S | 详情 | 详情 | |
| (VIII) | 37676 | [2-(dimethylamino)-6-methoxy-1-benzothiophen-3-yl][4-[2-(1-piperidinyl)ethoxy]phenyl]methanone | C25H30N2O3S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XI)Condensation of phenol (X) with N-(2-hydroxyethyl)piperidine (XI) under Mitsunobu conditions furnished ether (XII). The lactam function of (XII) was then reduced with LiAlH4 to produce (XIII). Finally, methyl ether cleavage in (XIII) was carried out by treatment with AlCl3 in the presence of EtSH.
| 【1】 Grese, T.A.; et al.; Photochemical synthesis of N-arylbenzophenanthridine selective estrogen receptor modulators (SERMs). J Med Chem 2001, 44, 17, 2857. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (X) | 50231 | 5-(4-hydroxyphenyl)-2,8-dimethoxybenzo[c]phenanthridin-6(5H)-one | C25H19NO4 | 详情 | 详情 | |
| (XI) | 37675 | 2-(1-piperidinyl)-1-ethanol | 3040-44-6 | C7H15NO | 详情 | 详情 |
| (XII) | 50233 | 4-[2,8-dimethoxybenzo[c]phenanthridin-5(6H)-yl]phenyl 2-(1-piperidinyl)ethyl ether; 2,8-dimethoxy-5-[4-[2-(1-piperidinyl)ethoxy]phenyl]-5,6-dihydrobenzo[c]phenanthridine | C32H34N2O3 | 详情 | 详情 | |
| (XIII) | 50232 | 2,8-dimethoxy-5-[4-[2-(1-piperidinyl)ethoxy]phenyl]benzo[c]phenanthridin-6(5H)-one | C32H32N2O4 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(II)By condensation of 2-heptoxyphenylisocyanate (I) with 2-piperidinoethanol (II) in dry toluene, followed by conversion into hydrochloride.
| 【1】 Kolwas, J.; Heptacaine. Drugs Fut 1979, 4, 7, 489. |
| 【2】 Cizmarik, J.; et al.; Pivotal BioSciences and ProteomTech collaborate on development of PB1. Pharmazie 1978, 33, 297. |