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【结 构 式】 
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【分子编号】60166 【品名】{4-[2-(1-azepanyl)ethoxy]phenyl}methanol 【CA登记号】 |
【 分 子 式 】C15H23NO2 【 分 子 量 】249.35316 【元素组成】C 72.25% H 9.3% N 5.62% O 12.83% |
合成路线1
该中间体在本合成路线中的序号：(IV)Alkylation of 4-hydroxybenzaldehyde (I) with chloro derivative (II) by means of K2CO3 in DMF at reflux affords benzaldehyde derivative (III), which is reduced with NaBH4 in MeOH to provide the benzylic alcohol (IV) --alternatively, alcohol (IV) can be obtained by reaction of 4-hydroxybenzyl alcohol (V) with chloro derivative (II) by means of NaOH and benzyltriethylammonium bromide in toluene--. Alcohol (V) is treated with HCl in THF and then chlorinated with SOCl2 to furnish hydrochloride salt (VI), which is condensed with the indole derivative (VII) – produced by condensation of the bromo ketone (VIII) and 4-benzyloxyaniline hydrochloride (IX) either refluxing by with DMF or with Et3N in refluxing DMF – by means of NaH in DMF to give the N-alkylated indole (X). Finally, the O-benzyl protecting groups of (X) are removed by transfer hydrogenolysis using cyclohexadiene and Pd/C.
| 【1】 Miller, C.P.; Collini, M.D.; Tran, B.D.; et al.; Design, synthesis, and preclinical characterization of novel, highly selective indole estrogens. J Med Chem 2001, 44, 11, 1654. |
| 【2】 Vid, G.; Potoski, J.R.; Raveendranath, P.; Zeldis, J.; Ren, J. (American Home Products Corp.); Novel aryloxy-alkyl-dialkylamines. EP 1025077; WO 9919293 . |
| 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) | 13433 | 4-Hydroxybenzaldehyde; p-Hydroxybenzaldehyde | 123-08-0 | C7H6O2 | 详情 | 详情 |
| (II) | 22918 | 1-(2-chloroethyl)azepane | C8H16ClN | 详情 | 详情 | |
| (III) | 60165 | 4-[2-(1-azepanyl)ethoxy]benzaldehyde | C15H21NO2 | 详情 | 详情 | |
| (IV) | 60166 | {4-[2-(1-azepanyl)ethoxy]phenyl}methanol | C15H23NO2 | 详情 | 详情 | |
| (V) | 29474 | 4-(hydroxymethyl)phenol; 4-hydroxyphenylmethanol 4-hydroxybenzenemethanol; 4-Hydroxybenzyl alcohol | 623-05-2 | C7H8O2 | 详情 | 详情 |
| (VI) | 60167 | 1-{2-[4-(chloromethyl)phenoxy]ethyl}azepane; 2-(1-azepanyl)ethyl 4-(chloromethyl)phenyl ether | C15H22ClNO | 详情 | 详情 | |
| (VII) | 38490 | 5-(benzyloxy)-2-[4-(benzyloxy)phenyl]-3-methyl-1H-indole; benzyl 4-[5-(benzyloxy)-3-methyl-1H-indol-2-yl]phenyl ether | C29H25NO2 | 详情 | 详情 | |
| (VIII) | 38489 | 4-Benzyloxy-alpha-bromopropiophenone; 1-[4-(benzyloxy)phenyl]-2-bromo-1-propanone; alpha-Bromo-4-benzyloxy propiophenone | 54081-45-9 | C16H15BrO2 | 详情 | 详情 |
| (IX) | 22460 | 4-(benzyloxy)aniline; 4-(benzyloxy)phenylamine | C13H13NO | 详情 | 详情 | |
| (X) | 38495 | 1-[4-[2-(1-azepanyl)ethoxy]benzyl]-5-(benzyloxy)-2-[4-(benzyloxy)phenyl]-3-methyl-1H-indole; 4-[1-[4-[2-(1-azepanyl)ethoxy]benzyl]-5-(benzyloxy)-3-methyl-1H-indol-2-yl]phenyl benzyl ether | C44H46N2O3 | 详情 | 详情 |