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【结 构 式】 
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【分子编号】36424 【品名】1-[4-(benzyloxy)phenyl]-2-bromo-1-ethanone 【CA登记号】 |
【 分 子 式 】C15H13BrO2 【 分 子 量 】305.17102 【元素组成】C 59.04% H 4.29% Br 26.18% O 10.49% |
合成路线1
该中间体在本合成路线中的序号：(I)The enantioselective reduction of the phenacyl bromide (I) by means of a culture of Rhodotolule rubra in water gives the a(R)-hydroxy enantiomer (II), which is treated with K2CO3 in refluxing ethanol to yield the chiral epoxide (III). The condensation of (III) with 2-(3,4-dimethoxyphenyl)ethylamine (IV) by means of N,O-bis(trimethylsilyl)acetamide (TMSA) in hot DMSO affords the benzylated precursor (V), which is finally deprotected by means of HCl in water to provide the target Denopamine.
| 【1】 Goswami, J.; et al.; A conventient stereoselective synthesis of (R)-(-)-denopamine and (R)-(-)-salmeterol. Tetrahedron Asymmetry 2001, 12, 24, 3343. |
| 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) | 36424 | 1-[4-(benzyloxy)phenyl]-2-bromo-1-ethanone | C15H13BrO2 | 详情 | 详情 | |
| (II) | 62589 | (1R)-1-[4-(benzyloxy)phenyl]-2-bromo-1-ethanol | C15H15BrO2 | 详情 | 详情 | |
| (III) | 62590 | (2R)-2-[4-(benzyloxy)phenyl]oxirane; benzyl 4-[(2R)oxiranyl]phenyl ether | C15H14O2 | 详情 | 详情 | |
| (IV) | 10098 | 2-(3,4-Dimethoxyphenyl)-1-ethanamine; 3,4-Dimethoxyphenethylamine; 2-(3,4-Dimethoxyphenyl)ethylamine | 120-20-7 | C10H15NO2 | 详情 | 详情 |
| (V) | 31687 | (1R)-1-[4-(benzyloxy)phenyl]-2-[(3,4-dimethoxyphenethyl)amino]-1-ethanol | C25H29NO4 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VII)The bromination of 4-benzyloxyacetophenone (VI) with Br2 in dioxane gives 4-benzyloxyphenacyl bromide (VII), which by reduction with NaBH4 in dioxane and epoxidation with NaOH water is converted into (I). The condensation of 4-benzyloxystyrene oxide (I) with 1,1-dimethyl-3-(2-methoxyphenyl)propylamine (II) in refluxing isopropanol gives 1-(4-benzyloxyphenyl)-2-[1,1-dimethyl-3-(2-methoxyphenyl)propylamino]ethanol (III), which is debenzylated by reduction with H2 over Pd/C in ethanol, and treated with HCl.
| 【1】 Olsson, O.A.T.; Persson, N.H.A.; Svensson, L.A.; Waldeck, C.B.; Wetterlin, K.J.L.; EP 0004835 . |
| 【2】 Castaner, J.; Blancafort, P.; Serradell, M.N.; D-2343. Drugs Fut 1982, 7, 1, 17. |
| 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) | 36425 | 2-[4-(benzyloxy)phenyl]oxirane; benzyl 4-(2-oxiranyl)phenyl ether | C15H14O2 | 详情 | 详情 | |
| (II) | 36422 | 3-(2-methoxyphenyl)-1,1-dimethylpropylamine; 4-(2-methoxyphenyl)-2-methyl-2-butanamine | C12H19NO | 详情 | 详情 | |
| (III) | 36426 | 1-[4-(benzyloxy)phenyl]-2-[[3-(2-methoxyphenyl)-1,1-dimethylpropyl]amino]-1-ethanol | C27H33NO3 | 详情 | 详情 | |
| (VI) | 36423 | 1-[4-(benzyloxy)phenyl]-1-ethanone | 54696-05-8 | C15H14O2 | 详情 | 详情 |
| (VII) | 36424 | 1-[4-(benzyloxy)phenyl]-2-bromo-1-ethanone | C15H13BrO2 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(IX)In a very close procedure, alkylation of 2-propylpyridine (I) was effected with 4-benzyloxyphenacyl bromide (IX). The resulting pyridinium salt (X) was cyclized with NaHCO3 to give (XI), which was then condensed with dimethyl acetylenedicarboxylate (V) as before to give the tricyclic system (XII). Hydrolysis of diester (XII) to diacid (XIII), followed by decarboxylation with copper in hot quinoline yielded (XIV). The benzyl protecting group of (XIV) was then removed by catalytic hydrogenolysis in the presence of Pd/C.
| 【1】 Wassermann, K.; Kanstrup, A.; Jorgensen, A.S.; Bain, S.; Naerum, L.; Jacobsen, P.; Christiansen, L.B.; Bury, P.S.; Thorpe, S.M.; Synthesis and pharmacology of a novel pyrrolo[2,1,5-cd] indolizine (NNC 45-0095), a high affinity non-steroidal agonist for the estrogen receptor. Bioorg Med Chem Lett 2000, 10, 4, 399. |
| 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) | 39281 | 2-propylpyridine | 622-39-9 | C8H11N | 详情 | 详情 |
| (V) | 24551 | Dimethyl acetylenedicarboxylate; Dimethyl 2-butynedioate;Acetylenedicarboxylic acid dimethyl ester | 762-42-5 | C6H6O4 | 详情 | 详情 |
| (IX) | 36424 | 1-[4-(benzyloxy)phenyl]-2-bromo-1-ethanone | C15H13BrO2 | 详情 | 详情 | |
| (X) | 39287 | 1-[2-[4-(benzyloxy)phenyl]-2-oxoethyl]-2-propylpyridinium bromide | C23H24BrNO2 | 详情 | 详情 | |
| (XI) | 39288 | benzyl 4-(1-ethyl-2-indolizinyl)phenyl ether; 2-[4-(benzyloxy)phenyl]-1-ethylindolizine | C23H21NO | 详情 | 详情 | |
| (XII) | 39289 | dimethyl 3-[4-(benzyloxy)phenyl]-4-ethylpyrrolo[2,1,5-cd]indolizine-1,2-dicarboxylate | C29H25NO5 | 详情 | 详情 | |
| (XIII) | 39290 | 3-[4-(benzyloxy)phenyl]-4-ethylpyrrolo[2,1,5-cd]indolizine-1,2-dicarboxylic acid | C27H21NO5 | 详情 | 详情 | |
| (XIV) | 39291 | 2-[4-(benzyloxy)phenyl]-1-ethylpyrrolo[2,1,5-cd]indolizine; benzyl 4-(1-ethylpyrrolo[2,1,5-cd]indolizin-2-yl)phenyl ether | C25H21NO | 详情 | 详情 |