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【结 构 式】 
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【分子编号】43812 【品名】1-(6-methoxy-2-naphthyl)-1-ethanone 【CA登记号】3900-45-6 |
【 分 子 式 】C13H12O2 【 分 子 量 】200.23708 【元素组成】C 77.98% H 6.04% O 15.98% |
合成路线1
该中间体在本合成路线中的序号：(I)A short, simple and economical process for large-scale preparation of nabumetone has been reported: Condensation of commercially available 2-acetyl-6-methoxynaphthalene (2-acetylnaroline) (I) with ethyl acetate (II) by means of potassium sec-butoxide (sec-BuOK) in DMSO gives the ketoenol (III), which is reduced with H2 over Pd/C in ethyl acetate with a catalytic amount of sulfuric acid.
| 【1】 Nageshwar, D.; Devi, A.S.; Reddy, G.O.; Sarma, M.R.; Reddy, G.B.; Vyas, K.; Prabhakar, C.; Reddy, C.M.; Babu, J.M.; Process research and structural studies on nabumetone. Org Process Res Dev 1999, 3, 2, 121. |
合成路线2
该中间体在本合成路线中的序号：(I)The condensation between 4-hydroxy-3-methoxy-5-methylbenzaldehyde (I) and 3-aminopyridine (II) yields the corresponding benzalimine (III). The phenolic hydroxyl group of (III) is then protected as the silyl ether (IV) by using t-butyldimethylsilyl chloride and imidazole. Condensation of imine (IV) with the lithium derivative of diethyl methylphosphonate (V) affords the beta-amino phosphonate (VI). Finally, desilylation of (VI) with tetrabutylammonium fluoride and acetic acid provides the target phenol.
| 【1】 Phan, H.T.; et al.; Synthesis of a new series of compounds with lipoprotein(a)-lowering activity, Part 3: beta-Substituted-beta-amino-ethylphosphonates. Drugs Fut 2002, 27, Suppl. A. |
| 【2】 Ife, R.J.; Nguyen, L.M.; Bentzen, C.L.; Diep, V.V.; Azoulay, R.; Phan, H.T.; Niesor, E.J. (Ilex Oncology Research-Europe SA); beta-Substd. beta-aminoethyl phosphonates. US 2002111488; WO 0234756 . |
| 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) | 43812 | 1-(6-methoxy-2-naphthyl)-1-ethanone | 3900-45-6 | C13H12O2 | 详情 | 详情 |
| (II) | 33327 | 3-Pyridinylamine; 3-Aminopyridine; 3-Pyridinamine | 462-08-8 | C5H6N2 | 详情 | 详情 |
| (III) | 58411 | 2-methoxy-6-methyl-4-[(3-pyridinylimino)methyl]phenol | C14H14N2O2 | 详情 | 详情 | |
| (IV) | 58412 | N-[(E)-(4-{[tert-butyl(dimethyl)silyl]oxy}-3-methoxy-5-methylphenyl)methylidene]-N-(3-pyridinyl)amine; N-[(E)-(4-{[tert-butyl(dimethyl)silyl]oxy}-3-methoxy-5-methylphenyl)methylidene]-3-pyridinamine | C20H28N2O2Si | 详情 | 详情 | |
| (V) | 38496 | diethyl methylphosphonate | 683-08-9 | C5H13O3P | 详情 | 详情 |
| (VI) | 58413 | diethyl 2-(4-{[tert-butyl(dimethyl)silyl]oxy}-3-methoxy-5-methylphenyl)-2-(3-pyridinylamino)ethylphosphonate | C25H41N2O5PSi | 详情 | 详情 |