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【结 构 式】 
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【分子编号】18571 【品名】2,2-dibutyl-5-hydroxy-3,4-dihydro-1(2H)-naphthalenone 【CA登记号】 |
【 分 子 式 】C18H26O2 【 分 子 量 】274.40324 【元素组成】C 78.79% H 9.55% O 11.66% |
合成路线1
该中间体在本合成路线中的序号：(IV)Alkylation of 5-methoxytetralone (I) with n-butyl iodide in the presence of lithium diisopropylamide (LDA) in dimethoxyethane afforded a mixture of mono- (II) and dialkylated (III) compounds that were separated by column chromatography. Hydrolysis of methoxy group of (III) by treatment with AlBr3 in refluxing benzene yielded phenol (IV), which was converted to ether (VI) by treatment with 2-(chloromethyl)quinoline (V) and K2CO3. The reduction of ketone (VI) with NaBH4 in MeOH provided racemic alcohol (VII). Resolution of racemate (VII) was performed by esterification with (S)-O-methylmandeloyl chloride (VIII), followed by chromatographic separation of the diastereomeric mixture. Then, basic hydrolysis of pure diastereomer (IX) provided the (+)-enantiomer. Alternatively, asymmetric reduction of tetralone (VI) with LiAlH4 in cold THF in the presence of the chiral auxiliary (S)-4-anilino-3-methylamino-1-butanol (X) or (S)-2-amino-3-methyl-1,1-diphenyl-1-butanol (XI) afforded (+)-alcohol (respectively).
| 【1】 Yatabe, T.; Kayakiri, H.; Kawai, Y.; Oku, T.; Tanaka, H.; Studies on 5-lipoxygenase inhibitors. II. Discovery, optical resolution and enantioselective synthesis of FR110302, a highly potent non-redox type 5-lipoxygenase inhibitor. Chem Pharm Bull 1998, 46, 10, 1556. |
| 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) | 18568 | 5-methoxy-3,4-dihydro-1(2H)-naphthalenone | 33892-75-0 | C11H12O2 | 详情 | 详情 |
| (II) | 18569 | 2-butyl-5-methoxy-3,4-dihydro-1(2H)-naphthalenone | C15H20O2 | 详情 | 详情 | |
| (III) | 18570 | 2,2-dibutyl-5-methoxy-3,4-dihydro-1(2H)-naphthalenone | C19H28O2 | 详情 | 详情 | |
| (IV) | 18571 | 2,2-dibutyl-5-hydroxy-3,4-dihydro-1(2H)-naphthalenone | C18H26O2 | 详情 | 详情 | |
| (V) | 13162 | 2-(Chloromethyl)quinoline; alpha-Chloroquinaldine | 4377-41-7 | C10H8ClN | 详情 | 详情 |
| (VI) | 18573 | 2,2-dibutyl-5-(2-quinolinylmethoxy)-3,4-dihydro-1(2H)-naphthalenone | C28H33NO2 | 详情 | 详情 | |
| (VII) | 18574 | 2,2-dibutyl-5-(2-quinolinylmethoxy)-1,2,3,4-tetrahydro-1-naphthalenol | C28H35NO2 | 详情 | 详情 | |
| (VIII) | 18575 | (2S)-2-methoxy-2-phenylethanoyl chloride | C9H9ClO2 | 详情 | 详情 | |
| (IX) | 18576 | 2,2-dibutyl-5-(2-quinolinylmethoxy)-1,2,3,4-tetrahydro-1-naphthalenyl (2S)-2-methoxy-2-phenylethanoate | C37H43NO4 | 详情 | 详情 | |
| (X) | 18577 | (3R)-4-anilino-3-(methylamino)-1-butanol | C11H18N2O | 详情 | 详情 | |
| (XI) | 18578 | 2-amino-1,1-diphenyl-1-pentanol | C17H21NO | 详情 | 详情 |