Acetyl chloride → HCID 15027407, compound

HRID 1195901Notes

Reaction equation

HRID 1195901 reaction equation
[Cl:1][C:2]1[CH:25]=[CH:24][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]([CH:19]([NH:21][OH:22])[CH3:20])=[C:9]2[CH3:23])=[O:7])=[CH:4][CH:3]=1.[C:26]([O-])(=[O:28])[CH3:27].[Na+].C(Cl)(=O)C>O1CCOCC1.O.C(OCC)(=O)C>[Cl:1][C:2]1[CH:25]=[CH:24][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]([CH:19]([N:21]([OH:22])[C:26](=[O:28])[CH3:27])[CH3:20])=[C:9]2[CH3:23])=[O:7])=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 6367Acetyl chlorideHCID 517045Sodium AcetateHCID 15027406HCID 15027406, compound2×

Product 1

HCID 15027407HCID 15027407, compoundYield 12.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 500 mg of 1-(4-chlorobenzoyl)-3-[1-(hydroxyamino)ethyl]-5-methoxy-2-methyl-1H-indole (crude product of Example 78) and 230 mg (2.8 mmol) of sodium acetate in 20 ml of 1,4-dioxane and 5 ml of water is added dropwise 90 μl (1.26 mmol) of acetyl chloride. The reaction mixture is stirred for 10 minutes, at which time it is diluted with ethyl acetate and washed twice with water and once with 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, eluting with a gradient of ethyl acetate:methylene chloride (3:7 to 1:1). A second chromatography (silica gel, ether), and finally recrystallization from methanol gives 71 mg (6.3% from oxime) of pure N-[1-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]ethyl]-N-hydroxyacetamide; mp softens at 90° C. then decomposes as the temperature increases.

Workup

  1. washwashed twice with water and once with a saturated solution of sodium chloride
  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
  6. washeluting with a gradient of ethyl acetate:methylene chloride (3:7 to 1:1)
  7. customA second chromatography (silica gel, ether), and finally recrystallization from methanol

Sources & evidence

ORD record
ord-01a3e4c880a54ca1b20daf58b49503c8
Source dataset
uspto-grants-1992_05
Patent number
US05112846

Reaction notes

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