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【结 构 式】 
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【分子编号】42498 【品名】3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzoic acid 【CA登记号】 |
【 分 子 式 】C12H12F2O4 【 分 子 量 】258.2216864 【元素组成】C 55.82% H 4.68% F 14.71% O 24.78% |
与该中间体有关的原料药合成路线共 1 条
合成路线1
该中间体在本合成路线中的序号：(IV)Condensation of the benzaldehyde derivative (I) with chlorodifluoromethane (II) by means of NaOH and benzyltrimethylammonium chloride (BTMA) in dioxane/water gives 3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzaldehyde (III), which is oxidized with NaClO2 and sulfamic acid in acetic acid to yield the corresponding benzoic acid derivative (IV). The reaction of (IV) with SOCl2 in refluxing toluene affords the acyl chloride (V), which is finally condensed with 3,5-dichloropyridin-4-amine (VI) by means of NaH in THF.
| 【1】 Castaner, J.; Leeson, P.A.; Sorbera, L.A.; Roflumilast. Drugs Fut 2000, 25, 12, 1261. |
| 【2】 Flockerzi, D.; Gutterer, B.; Hatzelmann, A.; Schudt, C.; Beume, R.; Kilian, U.; Wolf, H.P.O. (Byk Gulden Lomberg Chemische Fabrik GmbH); Fluoroalkoxy-substd. benzamides and their use as cyclic nucleotide phosphodiesterase inhibitors. EP 0706513; JP 1996512041; US 5712298; WO 9501338 . |
| 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) | 42496 | 3-(cyclopropylmethoxy)-4-hydroxybenzaldehyde | C11H12O3 | 详情 | 详情 | |
| (II) | 23985 | Chlorodifluoromethane; Chloro(difluoro)methane | 75-45-6 | CHClF2 | 详情 | 详情 |
| (III) | 42497 | 3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzaldehyde | C12H12F2O3 | 详情 | 详情 | |
| (IV) | 42498 | 3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzoic acid | C12H12F2O4 | 详情 | 详情 | |
| (V) | 42499 | 3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzoyl chloride | C12H11ClF2O3 | 详情 | 详情 | |
| (VI) | 25135 | 3,5-dichloro-4-pyridinamine; 4-amino-3,5-dichloropyridine | 22889-78-7 | C5H4Cl2N2 | 详情 | 详情 |
Extended Information