Ethyl Acetate → N-methyl-N-phenethyl-2-(4-benzyloxy-3-formylindol-1-yl)acetamide

HRID 129691Notes

Reaction equation

HRID 129691 reaction equation
[H-].[Na+].[CH2:3]([O:10][C:11]1[CH:19]=[CH:18][CH:17]=[C:16]2[C:12]=1[C:13]([CH:20]=[O:21])=[CH:14][NH:15]2)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[CH3:22][N:23]([CH2:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:24](=[O:27])[CH2:25]Br.C(OCC)(=O)C>O1CCCC1.[Cl-].[Na+].O>[CH3:22][N:23]([CH2:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:24](=[O:27])[CH2:25][N:15]1[C:16]2[C:12](=[C:11]([O:10][CH2:3][C:4]3[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=3)[CH:19]=[CH:18][CH:17]=2)[C:13]([CH:20]=[O:21])=[CH:14]1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 70158464-(benzyloxy)-1H-indole-3-carbaldehydeHCID 10753531N-methyl-N-phenethyl-2-bromoacetamide

Product 1

HCID 10741107N-methyl-N-phenethyl-2-(4-benzyloxy-3-formylindol-1-yl)acetamide

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 57417360Sodium chloride; waterSolvent

Procedure

To a suspension of sodium hydride (1.31 g, 80% suspension in mineral oil, 43.8 mM) in 65 ml of tetrahydrofuran (THF), cooled in an ice bath, is added dropwise a solution of 4-benzyloxyindole-3-carboxaldehyde (10.2 g, 39.8 mM) in 55 ml of THF. The mixture is stirred in the cooling bath for an additional 30 minutes; N-methyl-N-phenethyl-2-bromoacetamide (15.3 g, 59.7 mM) is then added. The resulting mixture is stirred at room temperature for 18 hours. Ethyl acetate and 50% brine is added and the layers are separated. The organic layer is washed with brine, dried over magnesium sulfate and concentrated in vacuo to give crude product as a beige oil. Purification on preparative HPLC (silica gel column, 20% ethyl acetate in methylene chloride) gives N-methyl-N-phenethyl-2-(4-benzyloxy-3-formylindol-1-yl)acetamide. (m.p. 120°-122° C.)

Workup

  1. temperaturecooled in an ice bath
  2. stirringThe resulting mixture is stirred at room temperature for 18 hours
  3. customthe layers are separated
  4. washThe organic layer is washed with brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customto give crude product as a beige oil
  8. customPurification on preparative HPLC (silica gel column, 20% ethyl acetate in methylene chloride)

Sources & evidence

ORD record
ord-3406eb353d184e8a859d8f4cfef8029d
Source dataset
uspto-grants-1995_11
Patent number
US05468898

Reaction notes

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