【结 构 式】 |
【分子编号】40290 【品名】N-[3-(3,4-dimethylphenyl)propyl]-2-(4-hydroxy-3-methoxyphenyl)acetamide 【CA登记号】 |
【 分 子 式 】C20H25NO3 【 分 子 量 】327.42344 【元素组成】C 73.37% H 7.7% N 4.28% O 14.66% |
合成路线1
该中间体在本合成路线中的序号:(IX)The condensation of 3,4-dimethylbenzyl chloride (I) with diethyl malonate (II) by means of sodium ethoxide ethanol gives the diethyl 2-(3,4-dimethylbenzyl)malonate (III), which by treatment with aqueous refluxing NaOH and the with refluxing aqueous sulfuric acid yields 3-(3,4-dimethylphenyl)propionic acid (IV). The reaction of (IV) with refluxing SOCl2 affords the corresponding acyl chloride (V), which is treated with ammonia providing the amide (VI). The reduction of (VI) with LiAlH4 in refluxing THF gives 3-(3,4-dimethylphenyl)propylamine (VII), which by condensation with 2-(4-hydroxy-3-methoxyphenyl)acetic acid (VIII) by heating at 150 C yields the corresponding amide (IX). The alkylation of the phenolic group of (IX) with 1,2-dibromoethane (X) and NaH in refluxing THF affords the 2-bromoethoxy derivative (XI), which by treatment with NaN3 and Bu4NBr in refluxing benzene gives the 2-azidoethoxy derivative (XII). Finally, this compound is reduced with H2 over Pd/C in ethyl acetate to afford the target compound.
【1】 Lee, J.-C.; Lee, K.-S.; Han, M.-S.; Jung, Y.S.; Choi, J.; Park, N.-S.; Ha, D.-C.; Seong, C.-M.; Lim, H.-J.; Choi, S.W.; Synthesis of homovanillic amide derivatives and their analgesic activity. Arch Pharmacal Res 1996, 19, 3, 246. |
【2】 Lim, H.-J.; Park, N.-S.; Choi, J.-K.; Ha, D.-C.; Kim, H.-S.; Lee, B.-Y.; N-Aralkylated 4-(2-aminoethoxy)phenylacetamide derivatives as potent analgesic and antiinflammatory agents. Korean Journal of Medicinal Chemistry 1991, 1, 1, 36. |
【3】 Lee, K.S.; Choi, J.K.; Hong, M.S.; Kim, H.S.; Lim, H.J.; Ha, D.C.; Park, N.S. (Korea Research Institute of Chemical Technology); Novel phenylacetamide derivs. and processes for the preparation thereof. EP 0525360; US 5242944 . |
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) | 40283 | 4-(chloromethyl)-1,2-dimethylbenzene | 102-46-5 | C9H11Cl | 详情 | 详情 |
(II) | 16829 | Diethyl malonate | 105-53-3 | C7H12O4 | 详情 | 详情 |
(III) | 40284 | diethyl 2-(3,4-dimethylbenzyl)malonate | C16H22O4 | 详情 | 详情 | |
(IV) | 40285 | 3-(3,4-dimethylphenyl)propionic acid | C11H14O2 | 详情 | 详情 | |
(V) | 40286 | 3-(3,4-dimethylphenyl)propanoyl chloride | C11H13ClO | 详情 | 详情 | |
(VI) | 40287 | 3-(3,4-dimethylphenyl)propanamide | C11H15NO | 详情 | 详情 | |
(VII) | 40288 | 3-(3,4-dimethylphenyl)-1-propanamine; 3-(3,4-dimethylphenyl)propylamine | C11H17N | 详情 | 详情 | |
(VIII) | 40289 | 4-Hydroxy-3-methoxyphenylacetic acid; Homovanillic acid; 2-(4-hydroxy-3-methoxyphenyl)acetic acid | 306-08-1 | C9H10O4 | 详情 | 详情 |
(IX) | 40290 | N-[3-(3,4-dimethylphenyl)propyl]-2-(4-hydroxy-3-methoxyphenyl)acetamide | C20H25NO3 | 详情 | 详情 | |
(X) | 10252 | 1,2-Dibromoethane; Ethylene dibromide | 106-93-4 | C2H4Br2 | 详情 | 详情 |
(XI) | 40291 | 2-[4-(2-bromoethoxy)-3-methoxyphenyl]-N-[3-(3,4-dimethylphenyl)propyl]acetamide | C22H28BrNO3 | 详情 | 详情 | |
(XII) | 40292 | 2-[4-(2-azidoethoxy)-3-methoxyphenyl]-N-[3-(3,4-dimethylphenyl)propyl]acetamide | C22H28N4O3 | 详情 | 详情 |