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【结 构 式】 
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【分子编号】31685 【品名】(2R)-2-[4-(benzyloxy)phenyl]-2-hydroxyethanoic acid; (2R)-4-benzyloxymandelic acid 【CA登记号】 |
【 分 子 式 】C15H14O4 【 分 子 量 】258.27376 【元素组成】C 69.76% H 5.46% O 24.78% |
合成路线1
该中间体在本合成路线中的序号：(III)The benzylation of 4-hydroxymandelic acid (I) with benzyl alcohol (II) and K2CO3 in methanol gives 4-benzyloxymandelic acid (III), which is condensed with 2-(3,4-dimethoxyphenyl)ethylamine (IV) by means of (C2H5O)2PON3 in THF to afford N-(3,4-dimethoxyphenylethyl)-4-benzyloxymandelamide (V). The reduction of (V) with diborane in THF yields the final product protected at the phenolic hydroxyl (VI) This compound is finally deprotected by hydrogenolysis with H2 over Pd/C.
| 【1】 Noguchi, K.; Irie, K.; Preparation of optically active benzyl alcohol derivative. JP 54070231 . |
| 【2】 Blancafort, P.; Castaner, J.; Serradell, M.N.; TA-064. Drugs Fut 1982, 7, 6, 407. |
| 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) | 31684 | (2R)-4-Hydroxymandelic acid; (2R)-2-Hydroxy-2-(4-hydroxyphenyl)ethanoic acid | 7198-10-9 | C8H8O4 | 详情 | 详情 |
| (II) | 18710 | Benzyl alcohol; Phenylmethanol | 100-51-6 | C7H8O | 详情 | 详情 |
| (III) | 31685 | (2R)-2-[4-(benzyloxy)phenyl]-2-hydroxyethanoic acid; (2R)-4-benzyloxymandelic acid | C15H14O4 | 详情 | 详情 | |
| (IV) | 10098 | 2-(3,4-Dimethoxyphenyl)-1-ethanamine; 3,4-Dimethoxyphenethylamine; 2-(3,4-Dimethoxyphenyl)ethylamine | 120-20-7 | C10H15NO2 | 详情 | 详情 |
| (V) | 31686 | (2R)-2-[4-(benzyloxy)phenyl]-N-(3,4-dimethoxyphenethyl)-2-hydroxyethanamide | C25H27NO5 | 详情 | 详情 | |
| (VI) | 31687 | (1R)-1-[4-(benzyloxy)phenyl]-2-[(3,4-dimethoxyphenethyl)amino]-1-ethanol | C25H29NO4 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)(R)-4-Hydroxymandelic acid (I) was protected as the benzyl ether (II) by treatment with benzyl bromide and K2CO3. Hydroxy acid (II) was then coupled with (S)-2-amino-7-hydroxytetralin (III) by means of BOP reagent to afford hydroxy amide (IV), which was subsequently reduced to amino alcohol (V) using borane-dimethyl sulfide complex. After protection of the aliphatic alcohol group of (V) with trifluoroacetic anhydride, the phenolic hydroxyl was alkylated with 2-bromo-N,N-dimethylacetamide in the presence of Cs2CO3 to furnish adduct (VII). Further deprotection of the trifluoroacetate ester of (VII) employing diethylamine yielded alcohol (VIII). Finally, hydrogenolysis of the benzyl ether (VIII) over Pd/C provided the title compound, which was isolated as the hydrochloride salt.
| 【1】 Kitazawa, M.; Okazaki, K.; Tamai, T.; Saito, M.; Muranaka, H.; Tanaka, N.; Kobayashi, H.; Kikuchi, K. (Kissei Pharmaceutical Co., Ltd.); Phenylethanolaminotetralincarboxamide derivs.. EP 0893432; US 6046192; WO 9738970 . |
| 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) | 31684 | (2R)-4-Hydroxymandelic acid; (2R)-2-Hydroxy-2-(4-hydroxyphenyl)ethanoic acid | 7198-10-9 | C8H8O4 | 详情 | 详情 |
| (II) | 31685 | (2R)-2-[4-(benzyloxy)phenyl]-2-hydroxyethanoic acid; (2R)-4-benzyloxymandelic acid | C15H14O4 | 详情 | 详情 | |
| (III) | 32819 | (7S)-7-amino-5,6,7,8-tetrahydro-2-naphthalenol | C10H13NO | 详情 | 详情 | |
| (V) | 44934 | (2R)-2-[4-(benzyloxy)phenyl]-2-hydroxy-N-[(2S)-7-hydroxy-1,2,3,4-tetrahydro-2-naphthalenyl]ethanamide | C25H25NO4 | 详情 | 详情 | |
| (VI) | 44935 | (7S)-7-([(2R)-2-[4-(benzyloxy)phenyl]-2-hydroxyethyl]amino)-5,6,7,8-tetrahydro-2-naphthalenol | C25H27NO3 | 详情 | 详情 | |
| (VII) | 44936 | (1R)-1-[4-(benzyloxy)phenyl]-2-([(2S)-7-[2-(dimethylamino)-2-oxoethoxy]-1,2,3,4-tetrahydro-2-naphthalenyl]amino)ethyl 2,2,2-trifluoroacetate | C31H33F3N2O5 | 详情 | 详情 | |
| (VIII) | 44937 | 2-[[(7S)-7-([(2R)-2-[4-(benzyloxy)phenyl]-2-hydroxyethyl]amino)-5,6,7,8-tetrahydro-2-naphthalenyl]oxy]-N,N-dimethylacetamide | C29H34N2O4 | 详情 | 详情 |