Ethyl vinyl ether → 6-Acetyl-3-{1-(1,3-benzodioxol-5-yl)-2-[(2-methoxy-4-methylphenyl)sulfonamido]-2-oxoethyl}-1-methyl-1H-indole

HRID 1934630Notes

Reaction equation

HRID 1934630 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([CH:10]([C:26]3[C:34]4[C:29](=[CH:30][C:31](Br)=[CH:32][CH:33]=4)[N:28]([CH3:36])[CH:27]=3)[C:11]([NH:13][S:14]([C:17]3[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][C:18]=3[O:24][CH3:25])(=[O:16])=[O:15])=[O:12])=[CH:9][C:4]=2[O:3][CH2:2]1.[CH:37]([O:39]CC)=[CH2:38].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(CC)CC)C>C(#N)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:37]([C:31]1[CH:30]=[C:29]2[C:34]([C:26]([CH:10]([C:8]3[CH:7]=[CH:6][C:5]4[O:1][CH2:2][O:3][C:4]=4[CH:9]=3)[C:11]([NH:13][S:14]([C:17]3[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][C:18]=3[O:24][CH3:25])(=[O:16])=[O:15])=[O:12])=[CH:27][N:28]2[CH3:36])=[CH:33][CH:32]=1)(=[O:39])[CH3:38]

Participants

7

Reactant 4

HCID 8023Ethyl vinyl etherHCID 8471TriethylamineHCID 80271Tri-o-tolylphosphineHCID 224672573-{1-(1,3-benzodioxol-5-yl)-2-[(2-methoxy-4-methylphenyl)sulfonamido]-2-oxoethyl}-6-bromo-1-methyl-1H-indole

Product 1

HCID 224672346-Acetyl-3-{1-(1,3-benzodioxol-5-yl)-2-[(2-methoxy-4-methylphenyl)sulfonamido]-2-oxoethyl}-1-methyl-1H-indole

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolvent

Procedure

A mixture of 3-{1-(1,3-benzodioxol-5-yl)-2-[(2-methoxy-4-methylphenyl)sulfonamido]-2-oxoethyl}-6-bromo-1-methyl-1H-indole (from Example 85, 300 mg, 0.53 mmol), ethyl vinyl ether (0.063 ml), palladium(II)acetate (6 mg), tri-o-tolylphosphine (13 mg) and triethylamine (0.1 ml) in acetonitrile (5 ml) was heated at reflux for 18 hours under a nitrogen atmosphere. After cooling, the solvent was evaporated in vacuo and the residue was stirred with 2N hydrochloric acid (˜6 ml) for 45 minutes. The mixture was twice extracted with ethyl acetate, and then washed with water, and brine. The organic layer was dried (magnesium sulphate) and the solvents were evaporated in vacuo. The residue was flash chromatographed using a gradient elution of a mixture of 90% hexane and 10% ethyl acetate, through to 40% hexane and 60% ethyl acetate, to give the title compound (80 mg).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 18 hours under a nitrogen atmosphere
  3. temperatureAfter cooling
  4. customthe solvent was evaporated in vacuo
  5. extractionThe mixture was twice extracted with ethyl acetate
  6. washwashed with water, and brine
  7. dry with materialThe organic layer was dried (magnesium sulphate)
  8. customthe solvents were evaporated in vacuo
  9. customchromatographed
  10. washa gradient elution of a mixture of 90% hexane and 10% ethyl acetate

Sources & evidence

ORD record
ord-bba6708181b3467a88545674ed3063e5
Source dataset
uspto-grants-2002_05
Patent number
US06384070B2

Reaction notes

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