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【结 构 式】 
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【分子编号】14048 【品名】(4-Hydroxy-3-methoxyphenyl)(4-methylphenyl)methanone 【CA登记号】 |
【 分 子 式 】C15H14O3 【 分 子 量 】242.27436 【元素组成】C 74.36% H 5.82% O 19.81% |
合成路线1
该中间体在本合成路线中的序号：(V)The synthesis of Ro 40-7592 is carried out as follows: Addition of 4-bromotoluene (I) to 4-(benzyloxy)-3-methoxybenzaldehyde (II) in the presence of butyllithium in THF at -78 C gives 4-(benzyloxy)-3-methoxy-4'-methylbenzhydrol (III). Oxidation of this compound with pyridinium chlorochromate in CH2Cl2 yields the corresponding 4-(benzyloxy)-3-methoxy-4'-methylbenzophenone (IV). Debenzylation of (IV) with 30% aqueous hydrobromic acid in acetic acid affords 4-hydroxy-3-methoxy-4'-methylbenzophenone (V). Regioselective nitration of (V) with 65% aqueous nitric acid in acetic acid gives 4-hydroxy-3-methoxy-4'-methyl-5-nitrobenzophenone (VI). Hydrolysis of the methoxy group in (VI) with 30% aqueous hydrobromic acid in boiling acetic acid affords 3,4-dihydroxy-4'-methyl-5-nitrobenzophenone, Ro 40-7592.
| 【1】 Bernauer, K.; Borgulya, J.; Bruderer, H.; Da Prada, M.; Zurcher, G. (F. Hoffmann-La Roche AG); 3,5-Disubstituted pyrocatechol derivs. EP 0237929; US 5389653; US 5476875 . |
| 【2】 Scherschlicht, R.; Schlappi, B.; Borgulya, J.; Dingemanse, J.; Da Prada, M.; Zurcher, G.; Ro 40-7592. Drugs Fut 1991, 16, 8, 719. |
| 【3】 Zurcher, G.; Da Prada, M.; Borgulya, J.; Bernauer, K.; Bruderer, H.; Catechol-O-methyltransferase-inhibiting pyrocatechol derivatives: Synthesis and structure-activity studies. Helv Chim Acta 1989, 72, 952-68. |
| 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) | 14044 | 4-Bromotoluene; 1-Bromo-4-methylbenzene | 106-38-7 | C7H7Br | 详情 | 详情 |
| (II) | 14045 | 4-(Benzyloxy)-3-methoxybenzaldehyde; 4-Benzyloxy-3-methoxybenzaldehyde | 2426-87-1 | C15H14O3 | 详情 | 详情 |
| (III) | 14046 | [4-(Benzyloxy)-3-methoxyphenyl](4-methylphenyl)methanol | C22H22O3 | 详情 | 详情 | |
| (IV) | 14047 | [4-(Benzyloxy)-3-methoxyphenyl](4-methylphenyl)methanone | C22H20O3 | 详情 | 详情 | |
| (V) | 14048 | (4-Hydroxy-3-methoxyphenyl)(4-methylphenyl)methanone | C15H14O3 | 详情 | 详情 | |
| (VI) | 14049 | (4-Hydroxy-3-methoxy-5-nitrophenyl)(4-methylphenyl)methanone | C15H13NO5 | 详情 | 详情 |