|
【结 构 式】 
|
【分子编号】43376 【品名】3-[3,5-di(tert-butyl)-4-hydroxyphenyl]propionic acid 【CA登记号】20170-32-5 |
【 分 子 式 】C17H26O3 【 分 子 量 】278.39164 【元素组成】C 73.35% H 9.41% O 17.24% |
合成路线1
该中间体在本合成路线中的序号：(II)Catalytic hydrogenation of 3,5-di-tert-butyl-4-hydroxycinnamic acid (I) afforded the saturated carboxylic acid (II), which was converted into amide (IV) via the corresponding acid chloride (III). Reduction of the amide function of (IV) by means of LiAlH4 furnished the primary amine (V). This was condensed with O-benzyl maltol (VI) to produce the pyridone (VII). After hydrogenolysis of the benzyl protecting group of (VII), the title compound was isolated as the corresponding mesylate salt.
| 【1】 Malcolm, C.S.; Bebbington, D.; Monck, N.J.T.; Palmer, A.M.; Gaur, S.; Benwell, K.; Porter, R.H.P.; Harvey, V.; 3,5-Disubstituted-4-hydroxyphenyls linked to 3-hydroxy-2-methyl-4(1H)-pyridinone: Potent inhibitors of lipid peroxidation and cell toxicity. J Med Chem 2000, 43, 15, 2779. |
| 【2】 Malcolm, C.; Porter, R.; Bebbington, D.; Palmer, A.; Gaur, S.; Monck, N. (Vernalis Research Ltd.); Ortho-hydroxypyridinone derivs. as iron chelating and antioxidant agents. EP 1027335; WO 9923075 . |
| 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) | 43375 | (E)-3-[3,5-di(tert-butyl)-4-hydroxyphenyl]-2-propenoic acid | 22014-01-3 | C17H24O3 | 详情 | 详情 |
| (II) | 43376 | 3-[3,5-di(tert-butyl)-4-hydroxyphenyl]propionic acid | 20170-32-5 | C17H26O3 | 详情 | 详情 |
| (III) | 43777 | 5,5,8,8-tetramethyl-N-(2-nitrophenyl)-5,6,7,8-tetrahydro-2-naphthalenamine; N-(2-nitrophenyl)-N-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthalenyl)amine | C20H24N2O2 | 详情 | 详情 | |
| (IV) | 43378 | 3-[3,5-di(tert-butyl)-4-hydroxyphenyl]propanamide | C17H27NO2 | 详情 | 详情 | |
| (V) | 43379 | 4-(3-aminopropyl)-2,6-di(tert-butyl)phenol | C17H29NO | 详情 | 详情 | |
| (VI) | 12074 | 3-(Benzyloxy)-2-methyl-4H-pyran-4-one；3-(benzyloxy)-2-methylpyran-4-one | 61049-69-2 | C13H12O3 | 详情 | 详情 |
| (VII) | 43380 | 3-(benzyloxy)-1-[3-[3,5-di(tert-butyl)-4-hydroxyphenyl]propyl]-2-methyl-4(1H)-pyridinone | C30H39NO3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)Reduction of 3-(3,5-di-t-butyl-4-hydroxyphenyl)propionic acid (I) with LiAlH4 afforded alcohol (II), which was further brominated to (III) using PBr3. Alkylation of p-nitrophenol (IV) by the alkyl bromide (III) gave ether (V). Then, reduction of the nitro group of (V) to the aniline (VI) was accomplished by means of hydrazine in the presence of Raney nickel.
| 【1】 Aubriot, S.; et al.; New series of aryloxypropanolamines with both human beta3-adrenoceptor agonistic activity and free radical scavenging properties. Bioorg Med Chem Lett 2002, 12, 2, 209. |
| 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) | 43376 | 3-[3,5-di(tert-butyl)-4-hydroxyphenyl]propionic acid | 20170-32-5 | C17H26O3 | 详情 | 详情 |
| (II) | 41518 | 2,6-di(tert-butyl)-4-(3-hydroxypropyl)phenol | C17H28O2 | 详情 | 详情 | |
| (III) | 59677 | 4-(3-bromopropyl)-2,6-di(tert-butyl)phenol | C17H27BrO | 详情 | 详情 | |
| (IV) | 11236 | 4-Nitrophenol; p-Nitrophenol | 100-02-7 | C6H5NO3 | 详情 | 详情 |
| (V) | 59678 | 2,6-di(tert-butyl)-4-[3-(4-nitrophenoxy)propyl]phenol | C23H31NO4 | 详情 | 详情 | |
| (VI) | 59679 | 4-[3-(4-aminophenoxy)propyl]-2,6-di(tert-butyl)phenol | C23H33NO2 | 详情 | 详情 |