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【结 构 式】 
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【分子编号】33328 【品名】2-(p-Benzyloxyphenyl)ethanol; 2-[4-(Benzyloxy)phenyl]-1-ethanol 【CA登记号】 |
【 分 子 式 】C15H16O2 【 分 子 量 】228.29084 【元素组成】C 78.92% H 7.06% O 14.02% |
合成路线1
该中间体在本合成路线中的序号：(IV)The condensation of ethyl p-hydroxyphenylacetate (I) with benzyl chloride (II) by means of sodium ethoxide in refluxing ethanol gives ethyl p-(benzyloxy)phenylacetate (III), which is reduced with LiAlH4 in THF to 2-(p-benzyloxyphenyl)ethanol (IV). The etherification of (IV) with cyclopropyl bromide (A) by means of NaH in hot DMF affords 4-(cyclopropylmethoxyethyl)-1-benzyloxybenzene (V), which is debenzylated by hydrogenation with H2 and Pd/C in methanol giving rise to p-(cyclopropylmethoxyethyl)phenol (VI). The condensation of (VI) with epichlorohydrin (B) by means of NaOH in water yields 1-[p-(cyclopropylmethoxyethyl)phenoxy]-2,3-epoxypropane (VII), which is treated with isopropylamine (C) and finally with HCl in ether.
| 【1】 Manoury, P.M.J.; et al. (Sanofi-Synthelabo ); Phenol ethers. DE 2649605; FR 2330383; GB 1515978; JP 52085146; US 4252984 . |
| 【2】 Hillier, K.; Castaner, J.; Serradell, M.N.; Blancafort, P.; Betaxolol hydrochloride. Drugs Fut 1979, 4, 12, 867. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (B) | 10146 | Epichlorohydrin; 2-(Chloromethyl)oxirane | 106-89-8 | C3H5ClO | 详情 | 详情 |
| (A) | 22277 | Cyclopropyl bromide; 1-(Bromomethyl)cyclopropane | 7051-34-5 | C4H7Br | 详情 | 详情 |
| (I) | 24994 | Ethyl 2-(4-hydroxyphenyl)acetate | 17138-28-2 | C10H12O3 | 详情 | 详情 |
| (II) | 19171 | 1-(Chloromethyl)benzene; Benzyl chloride | 100-44-7 | C7H7Cl | 详情 | 详情 |
| (III) | 28637 | Ethyl 2-[4-(benzyloxy)phenyl]acetate; p-(Benzyloxy)phenylacetate | C17H18O3 | 详情 | 详情 | |
| (IV) | 33328 | 2-(p-Benzyloxyphenyl)ethanol; 2-[4-(Benzyloxy)phenyl]-1-ethanol | C15H16O2 | 详情 | 详情 | |
| (V) | 33329 | 4-(Cyclopropylmethoxyethyl)-1-benzyloxybenzene; 1-(Benzyloxy)-4-[2-(cyclopropylmethoxy)ethyl]benzene; Benzyl 4-[2-(cyclopropylmethoxy)ethyl]phenyl ether | C19H22O2 | 详情 | 详情 | |
| (VI) | 33330 | 4-[2-(Cyclopropylmethoxy)ethyl]phenol; p-(Cyclopropylmethoxyethyl)phenol | C12H16O2 | 详情 | 详情 | |
| (VII) | 33331 | 2-([4-[2-(Cyclopropylmethoxy)ethyl]phenoxy]methyl)oxirane; 1-[p-(Cyclopropylmethoxyethyl)phenoxy]-2,3-epoxypropane; 4-[2-(Cyclopropylmethoxy)ethyl]phenyl 2-oxiranylmethyl ether | C15H20O3 | 详情 | 详情 | |
| (C) | 23933 | 2-Propanamine; Isopropylamine | 75-31-0 | C3H9N | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VII)The intermediate carboxylic acid (XIII) was prepared as follows: 2-(4-Hydroxyphenyl)ethanol (VI) was selectively protected at the phenolic hydroxyl with benzyl bromide, yielding (VII). Subsequent oxidation of the aliphatic alcohol group of (VII) with Dess-Martin periodinane reagent provided aldehyde (VIII). Wadsworth-Emmons condensation of (VIII) with the sodium derivative of phosphonate (IX) furnished adduct (X), which was further hydrogenated over Pd/C to the saturated ester (XI). The phenolic hydroxyl group of (XI), which was concomitantly debenzylated in the preceding hydrogenation step, was further reprotected as the methoxymethyl ether (XII). Acid (XIII) was then obtained by basic hydrolysis of ester (XII).
| 【1】 Takaoka, E.; et al.; Catalytic asymmetric synthesis of arbutamine. Heterocycles 1997, 46, 157. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VI) | 47355 | 4-(2-hydroxyethyl)phenol | 501-94-0 | C8H10O2 | 详情 | 详情 |
| (VII) | 33328 | 2-(p-Benzyloxyphenyl)ethanol; 2-[4-(Benzyloxy)phenyl]-1-ethanol | C15H16O2 | 详情 | 详情 | |
| (VIII) | 55597 | 2-[4-(benzyloxy)phenyl]acetaldehyde | C15H14O2 | 详情 | 详情 | |
| (IX) | 10019 | Ethyl 2-(diethoxyphosphoryl)acetate; Triethyl phosphonoacetate | 867-13-0 | C8H17O5P | 详情 | 详情 |
| (X) | 55598 | ethyl (E)-4-[4-(benzyloxy)phenyl]-2-butenoate | C19H20O3 | 详情 | 详情 | |
| (XI) | 55599 | ethyl 4-(4-hydroxyphenyl)butanoate | C12H16O3 | 详情 | 详情 | |
| (XII) | 55600 | ethyl 4-[4-(methoxymethoxy)phenyl]butanoate | C14H20O4 | 详情 | 详情 | |
| (XIII) | 55601 | 4-[4-(methoxymethoxy)phenyl]butanoic acid | C12H16O4 | 详情 | 详情 |