|
【结 构 式】 
|
【分子编号】59404 【品名】1-[4-(benzyloxy)-3-methoxyphenyl]-2-phenyl-1-ethanone 【CA登记号】 |
【 分 子 式 】C22H20O3 【 分 子 量 】332.399 【元素组成】C 79.5% H 6.06% O 14.44% |
合成路线1
该中间体在本合成路线中的序号：(IV)Protection of vanillin (I) as the benzyl ether (II), followed by reaction with benzylmagnesium bromide, furnished alcohol (III). Oxidation of alcohol (III) to the corresponding ketone (IV) was achieved by means of chromium trioxide or, in an improved procedure, by Oppenauer oxidation with cyclohexanone and sodium tert-butoxide. Benzyl group cleavage in (IV) either with HBr, or by transfer hydrogenolysis, yielded phenol (V). Regioselective nitration of (V) gave the ortho-nitrophenol (VI). The title compound was finally obtained by methyl ether cleavage in (VI) with boiling HBr or with AlCl3 in pyridine.
| 【1】 Benes, J.; Vieira-Coelho, M.A.; Borges, N.; Freitas, A.P.; Soares-da-Silva, P.; Alves, P.C.; Learmonth, D.A.; Synthesis of 1-(3,4-dihydroxy-5-nitrophenyl)-2-phenyl-ethanone and derivatives as potent and long-acting peripheral inhibitors of catechol-O-methyltransferase. J Med Chem 2002, 45, 3, 685. |
| 【3】 Benes, J.; Soares da Silva, P.M.V.A.; Learmonth, D.A. (Portela & Ca., SA); Substd. 2-phenyl-1-(3,4-dihydroxy-5-nitrophenyl)-1-ethanones, their use in the treatment of some central and peripheral nervous system disorders and pharmaceutical compsns. containing them. EP 1010688; GB 2344819; WO 0037423 . |
| 【2】 Learmonth, D.; et al.; Synthesis of 1-(3,4-dihydroxy-5-nitrophenyl)-2-phenyl-ethanone and derivatives as potent and selective inhibitors of catechol-O-methyltransferase (COMT). 16th Int Symp Med Chem (Sept 18 2000, Bologna) 2000, Abst PA-34. |
| 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) | 22701 | 4-hydroxy-3-methoxybenzaldehyde | 121-33-5 | C8H8O3 | 详情 | 详情 |
| (II) | 14045 | 4-(Benzyloxy)-3-methoxybenzaldehyde; 4-Benzyloxy-3-methoxybenzaldehyde | 2426-87-1 | C15H14O3 | 详情 | 详情 |
| (III) | 59403 | 1-[4-(benzyloxy)-3-methoxyphenyl]-2-phenyl-1-ethanol | C22H22O3 | 详情 | 详情 | |
| (IV) | 59404 | 1-[4-(benzyloxy)-3-methoxyphenyl]-2-phenyl-1-ethanone | C22H20O3 | 详情 | 详情 | |
| (V) | 59405 | 1-(4-hydroxy-3-methoxyphenyl)-2-phenyl-1-ethanone | C15H14O3 | 详情 | 详情 | |
| (VI) | 59406 | 1-(4-hydroxy-3-methoxy-5-nitrophenyl)-2-phenyl-1-ethanone | C15H13NO5 | 详情 | 详情 |