Sodium Hydroxide → (RS)-1-(5-methoxy-2,3-dihydro-1H-indol-2-ylmethyl)-4-(4-methyl-benzyl)-piperidin-4-ol

HRID 278439노트

반응식

HRID 278439 반응식
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8](S(C1C=CC(C)=CC=1)(=O)=O)[CH:7]([CH2:22][N:23]1[CH2:28][CH2:27][C:26]([CH2:30][C:31]3[CH:36]=[CH:35][C:34]([CH3:37])=[CH:33][CH:32]=3)([OH:29])[CH2:25][CH2:24]1)[CH2:6]2.[H-].COCCO[Al+]OCCOC.[Na+].[H-].[OH-].[Na+]>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]([CH2:22][N:23]1[CH2:28][CH2:27][C:26]([CH2:30][C:31]3[CH:32]=[CH:33][C:34]([CH3:37])=[CH:35][CH:36]=3)([OH:29])[CH2:25][CH2:24]1)[CH2:6]2

참가 물질

5

반응물 3

HCID 14798Sodium HydroxideHCID 21584525Sodium bis(2-methoxyethoxy)aluminiumhydrideHCID 22628326(RS)-1-[5-methoxy-1-(toluene-4-sulfonyl)-2,3-dihydro-1H-indol-2-ylmethyl]-4-(4-methyl-benzyl)-piperidin-4-ol

생성물 1

HCID 22628339(RS)-1-(5-methoxy-2,3-dihydro-1H-indol-2-ylmethyl)-4-(4-methyl-benzyl)-piperidin-4-ol수율 75.2%

시약·촉매·용매 1

HCID 1140Toluene용매

실험 절차

To a solution of (RS)-1-[5-methoxy-1-(toluene-4-sulfonyl)-2,3-dihydro-1H-indol-2-ylmethyl]-4-(4-methyl-benzyl)-piperidin-4-ol (300 mg, 0.576 mmol) in toluene (15 ml) was added sodium bis(2-methoxy-ethoxy) aluminium hydride (3.5 M in THF) (0.66 ml, 2.31 mmol), and the mixture refluxed 18 hr. After cooling, 2N NaOH was added to pH 14, the mixture was extracted with EtOAc (3x 25ml) and the combined extracts washed with satd. NaCl (25 ml), dried with (Na2SO4) then filtered and evaporated. The residue was chromatographed over SiO2 (Merck 230-400 mesh) eluting with EtOAc-cyclohexane-Et3N (9:10:1) to afford (RS)-1-(5-methoxy-2,3-dihydro-1H-indol-2-ylmethyl)-4-(4-methyl-benzyl)-piperidin-4-ol as a viscous yellow oil (158.4 mg, 0.433 mmol, 75%), MS: m/e=367.3 (M+H+).

후처리

  1. temperaturethe mixture refluxed 18 hr
  2. temperatureAfter cooling
  3. extractionthe mixture was extracted with EtOAc (3x 25ml)
  4. washthe combined extracts washed with satd
  5. dry with materialNaCl (25 ml), dried with (Na2SO4)
  6. filtrationthen filtered
  7. customevaporated
  8. customThe residue was chromatographed over SiO2 (Merck 230-400 mesh)
  9. washeluting with EtOAc-cyclohexane-Et3N (9:10:1)

출처 및 근거

ORD 기록
ord-58771e84ee0b4e4a9a0978a11855d7c7
출처 데이터셋
uspto-grants-2002_03
특허 번호
US06359138B1

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