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alpha-Bromo-o-chlorotoluene → (4-benzyl-4-hydroxy-piperidin-1-yl)-[1-(2-chloro-benzyl)-2-methyl-1H-indol-3-yl]-methanone

HRID 505084
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HRID 505084 반응식
[CH2:1]([C:8]1([OH:26])[CH2:13][CH2:12][N:11]([C:14]([C:16]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[NH:18][C:17]=2[CH3:25])=[O:15])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].Br[CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[Cl:37]>CN(C=O)C>[CH2:1]([C:8]1([OH:26])[CH2:9][CH2:10][N:11]([C:14]([C:16]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[N:18]([CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=3[Cl:37])[C:17]=2[CH3:25])=[O:15])[CH2:12][CH2:13]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
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참가 물질

5

반응물 3

HCID 11905alpha-Bromo-o-chlorotolueneHCID 24758Sodium hydrideHCID 66744648(4-benzyl-4-hydroxy-piperidin-1-yl)-(2-methyl-1H-indol-3-yl)-methanone

생성물 1

HCID 59429625(4-benzyl-4-hydroxy-piperidin-1-yl)-[1-(2-chloro-benzyl)-2-methyl-1H-indol-3-yl]-methanone수율 63.4%

시약·촉매·용매 1

HCID 6228Dimethylformamide
용매

실험 절차

To a stirred solution of 40 mg (0.11 mmol) of (4-benzyl-4-hydroxy-piperidin-1-yl)-(2-methyl-1H-indol-3-yl)-methanone in 5 ml DMF were added 5 mg (0.11 mmol) NaH (60% in oil). The mixture was stirred at RT for 30 min. and then 28 mg (0.13 mmol) of 1-bromomethyl-2-chloro-benzene were added. The mixture was stirred an additional hour and then poured onto water and extracted with ethyl acetate. The combined organic phases were dried over Na2SO4 and concentrated in vacuo. Preparative HPLC (30% CH3CN/H2O) afforded 33 mg (61%) of (4-benzyl-4-hydroxy-piperidin-1-yl)-[1-(2-chloro-benzyl)-2-methyl-1H-indol-3-yl]-methanone as a white solid.

후처리

  1. stirringThe mixture was stirred an additional hour
  2. additionpoured onto water
  3. extractionextracted with ethyl acetate
  4. dry with materialThe combined organic phases were dried over Na2SO4
  5. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-139efdfcfa5149de81f9f9bee22483ee
출처 데이터셋
uspto-grants-2010_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07781436B2

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