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【结 构 式】 
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【分子编号】46522 【品名】1-[2-[4-(chloromethyl)phenoxy]ethyl]piperidine; 4-(chloromethyl)phenyl 2-(1-piperidinyl)ethyl ether 【CA登记号】 |
【 分 子 式 】C14H20ClNO 【 分 子 量 】253.77164 【元素组成】C 66.26% H 7.94% Cl 13.97% N 5.52% O 6.3% |
合成路线1
该中间体在本合成路线中的序号：(V)Alkylation of p-hydroxybenzaldehyde (I) with 1-(2-chloroethyl)piperidine (II) afforded 4-(2-piperidinylethoxy)benzaldehyde (III). Aldehyde function reduction using NaBH4 provided the benzylic alcohol (IV). Alternatively, alcohol (IV) can be obtained by reaction of 4-hydroxybenzyl alcohol (A) with 1-(2-chloroethyl)piperidine hydrochloride (II) by means of NaOH and benzyl triethylammonium bromide in toluene.The hydrochloride salt of (IV) was then treated with SOCl2 to furnish chloride (V).
| 【1】 Silvestre, J.S.; Sorbera, L.A.; Castaner, J.; Pipendoxifene. Drugs Fut 2002, 27, 10, 942. |
| 【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 |
|---|---|---|---|---|---|---|
| (A) | 29474 | 4-(hydroxymethyl)phenol; 4-hydroxyphenylmethanol 4-hydroxybenzenemethanol; 4-Hydroxybenzyl alcohol | 623-05-2 | C7H8O2 | 详情 | 详情 |
| (I) | 13433 | 4-Hydroxybenzaldehyde; p-Hydroxybenzaldehyde | 123-08-0 | C7H6O2 | 详情 | 详情 |
| (II) | 10117 | 1-(2-Chloroethyl)piperidine; N-(2-Chloroethyl)piperidine | 1932-03-2 | C7H14ClN | 详情 | 详情 |
| (III) | 35795 | 4-[2-(1-piperidinyl)ethoxy]benzaldehyde | 26815-04-3 | C14H19NO2 | 详情 | 详情 |
| (IV) | 35796 | [4-[2-(1-piperidinyl)ethoxy]phenyl]methanol | C14H21NO2 | 详情 | 详情 | |
| (V) | 46522 | 1-[2-[4-(chloromethyl)phenoxy]ethyl]piperidine; 4-(chloromethyl)phenyl 2-(1-piperidinyl)ethyl ether | C14H20ClNO | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(V)Condensation between p-benzyloxyaniline (VI) and bromo ketone (VII) in refluxing DMF produced the indole derivative (VIII). Alkylation of (VIII) with chloride (V) in the presence of NaH gave the N-alkylated indole (IX). The O-benzyl protecting groups of (IX) were then removed by transfer hydrogenolysis using cyclohexadiene and Pd/C.
| 【1】 Silvestre, J.S.; Sorbera, L.A.; Castaner, J.; Pipendoxifene. Drugs Fut 2002, 27, 10, 942. |
| 【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 |
|---|---|---|---|---|---|---|
| (V) | 46522 | 1-[2-[4-(chloromethyl)phenoxy]ethyl]piperidine; 4-(chloromethyl)phenyl 2-(1-piperidinyl)ethyl ether | C14H20ClNO | 详情 | 详情 | |
| (VI) | 22460 | 4-(benzyloxy)aniline; 4-(benzyloxy)phenylamine | C13H13NO | 详情 | 详情 | |
| (VII) | 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 |
| (VIII) | 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 | |
| (IX) | 46523 | 5-(benzyloxy)-2-[4-(benzyloxy)phenyl]-3-methyl-1-[4-[2-(1-piperidinyl)ethoxy]benzyl]-1H-indole; benzyl 4-(5-(benzyloxy)-3-methyl-1-[4-[2-(1-piperidinyl)ethoxy]benzyl]-1H-indol-2-yl)phenyl ether | C43H44N2O3 | 详情 | 详情 |