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

HRID 278439Notes

Reaction equation

HRID 278439 reaction equation
[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

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 21584525Sodium bis(2-methoxyethoxy)aluminiumhydrideHCID 22628326HCID 22628326, compound

Product 1

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

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

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+).

Workup

  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)

Sources & evidence

ORD record
ord-58771e84ee0b4e4a9a0978a11855d7c7
Source dataset
uspto-grants-2002_03
Patent number
US06359138B1

Reaction notes

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