Acetyl chloride → N-[1-(4-Chloro-benzoyl)-5-methoxy-2-methyl-1H-indol-3-ylmethyl]-N-hydroxy-acetamide

HRID 703223Notes

Reaction equation

HRID 703223 reaction equation
[Cl:1][C:2]1[CH:24]=[CH:23][C:5]([C:6]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([O:17][CH3:18])=[CH:14][CH:15]=3)[C:10]([CH2:19][NH:20][OH:21])=[C:9]2[CH3:22])=[O:7])=[CH:4][CH:3]=1.[C:25]([O-])(=[O:27])[CH3:26].[Na+].C(Cl)(=O)C>O1CCOCC1.O.C(OCC)(=O)C>[Cl:1][C:2]1[CH:24]=[CH:23][C:5]([C:6]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([O:17][CH3:18])=[CH:14][CH:15]=3)[C:10]([CH2:19][N:20]([OH:21])[C:25](=[O:27])[CH3:26])=[C:9]2[CH3:22])=[O:7])=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 6367Acetyl chloride2×HCID 517045Sodium AcetateHCID 150273901-(4-Chlorobenzoyl)-N-hydroxy-5-methoxy-2-methyl-1H-indole-3-methanamine

Product 1

HCID 15027391N-[1-(4-Chloro-benzoyl)-5-methoxy-2-methyl-1H-indol-3-ylmethyl]-N-hydroxy-acetamideYield 47.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a suspension of 1-(4-chlorobenzoyl)-N-hydroxy-5-methoxy-2-methyl-1H-indole-3-methanamine (1,2 g, 3.5 mmol) and sodium acetate (730 mg, 8.9 mmol) in 120 ml of 1,4-dioxane and 30 ml of water is added dropwise acetyl chloride (420 μl, 5.9 mmol) at 0° C. After 10 minutes additional acetyl chloride (40 μl, 0.6 mmol) is added. The reaction mixture is stirred for 15 minutes, and then is diluted with ethyl acetate. It is washed once with a dilute solution of sodium bicarbonate, once with water, and a saturated solution of sodium chloride. The organic phase is further dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue is purified by column chromatography on silica gel, eluting first with 1:4 ethyl acetate:methylene chloride then 1:1 ethyl acetate:methylene chloride. Recrystallization from isopropyl ether gives N-[[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]methyl]-N-hydroxy-acetamide (645 mg, 47%); mp 160°-161° C.

Workup

  1. washIt is washed once with a dilute solution of sodium bicarbonate, once with water
  2. dry with materialThe organic phase is further dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue is purified by column chromatography on silica gel
  6. washeluting first with 1:4 ethyl acetate
  7. customRecrystallization from isopropyl ether

Sources & evidence

ORD record
ord-95e1fdd85b27457bbbeb0cf16eb81997
Source dataset
uspto-grants-1991_01
Patent number
US04981865

Reaction notes

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