Sodium Hydroxide → 3-{1-(1,3-Benzodioxol-5-yl)-2-[(2-methoxy-4-methylphenyl)sulfonamido]-2-oxoethyl}-5-(hydroxymethyl)-1-methyl-1H-indole

HRID 1934629Notes

Reaction equation

HRID 1934629 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][CH:31]=[C:32](Br)[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.[OH:37][CH2:38][Sn](CCCC)(CCCC)CCCC.[OH-].[Na+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Pd]>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([CH:10]([C:26]3[C:34]4[C:29](=[CH:30][CH:31]=[C:32]([CH2:38][OH:37])[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

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 41935931-(Tributylstannyl)methanolHCID 224672163-{1-(1,3-Benzodioxol-5-yl)-2-[(2-methoxy-4-methylphenyl)sulfonamido]-2-oxoethyl}-5-bromo-1-methyl-1H-indole

Product 1

HCID 224672363-{1-(1,3-Benzodioxol-5-yl)-2-[(2-methoxy-4-methylphenyl)sulfonamido]-2-oxoethyl}-5-(hydroxymethyl)-1-methyl-1H-indoleYield 12.6%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 3-{1-(1,3-benzodioxol-5-yl)-2-[(2-methoxy-4-methylphenyl)sulfonamido]-2-oxoethyl}-5-bromo-1-methyl-1H-indole (from Example 79, 300 mg, 0.53 mmol) in 1,4-dioxane (1.5 ml) under a nitrogen atmosphere was added hydroxymethyltributylstannane (253 mg, 0.79 mmol), followed by tetrakis(triphenylphosphine)palladium(O) (30 mg). The mixture was heated to reflux for 8 hours, and then cooled. Sodium hydroxide solution (1M) was added and the mixture boiled to dissolve the product. The solution was decanted clear of an insoluble tar residue, and washed with diethyl ether. After acidification with concentrated hydrochloric acid, the aqueous mixture was extracted with ethyl acetate. The organic extract was dried (magnesium sulphate) and the solvents were evaporated in vacuo. The residue was flash chromatographed using 2% methanol in dichloromethane as eluant to give the title compound (35 mg).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 8 hours
  3. temperaturecooled
  4. dissolutionto dissolve the product
  5. customThe solution was decanted clear of an insoluble tar residue
  6. washwashed with diethyl ether
  7. extractionAfter acidification with concentrated hydrochloric acid, the aqueous mixture was extracted with ethyl acetate
  8. extractionThe organic extract
  9. dry with materialwas dried (magnesium sulphate)
  10. customthe solvents were evaporated in vacuo
  11. customchromatographed

Sources & evidence

ORD record
ord-176d7bf3b332417a9bbe322d1f54ca37
Source dataset
uspto-grants-2002_05
Patent number
US06384070B2

Reaction notes

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