2-Butene, 1-bromo- → Methyl 3-[3-t-butylthio-1-(4-chlorobenzyl)-4-crotyl-5-hydroxyindol-2-yl]-2,2-dimethylpropanoate

HRID 1590109Notes

Reaction equation

HRID 1590109 reaction equation
[C:1]([S:5][C:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([OH:15])[CH:13]=2)[N:8]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)[C:7]=1[CH2:24][C:25]([CH3:31])([CH3:30])[C:26]([O:28][CH3:29])=[O:27])([CH3:4])([CH3:3])[CH3:2].[CH2:32](Br)[CH:33]=[CH:34][CH3:35]>CC1C=CC(C)=CC=1.[Cl-].[Cl-].[Zn+2]>[C:1]([S:5][C:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([OH:15])[C:13]=2[CH2:32][CH:33]=[CH:34][CH3:35])[N:8]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)[C:7]=1[CH2:24][C:25]([CH3:31])([CH3:30])[C:26]([O:28][CH3:29])=[O:27])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 1224142-Butene, 1-bromo-HCID 14980577Methyl 3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-hydroxy-1H-indol-2-yl)-2,2-dimethylpropanoate

Product 1

HCID 54549141Methyl 3-[3-t-butylthio-1-(4-chlorobenzyl)-4-crotyl-5-hydroxyindol-2-yl]-2,2-dimethylpropanoate

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 7809P-XyleneSolvent

Procedure

To a suspension of KH (35% dispersion in oil, 547 mg, 4.78 mmol) in p-xylene (20 mL) there was added methyl 3-[3-tert-butylthio-1-(4-chlorobenzyl)-5-hydroxyindol-2-yl]-2,2-dimethylpropanoate from Example 1, Method A, Step 3 (2.0 g, 4.35 mmol) and the mixture was refluxed for 20 minutes; after cooling, there was added freshly fused ZnCl2 (68 mg, 0.5 mmol) and the mixture was again refluxed for one hour, then cooled down to r.t. To the solution was added crotyl bromide (882 mg, 6.53 mmol) and stirring was continued at room temperature overnight. The mixture was quenched with saturated aqueous NH4Cl (20 mL) and 2 mL of 1N HCl. The organic phase was collected and the aqueous phase extracted with EtOAc. The combined organic phases were washed with H2O 3 times, dried and evaporated. The residue was chromatographed to afford the title compound as the minor component, as a yellow oil.

Workup

  1. temperaturethe mixture was refluxed for 20 minutes
  2. temperatureafter cooling
  3. temperaturethe mixture was again refluxed for one hour
  4. customThe mixture was quenched with saturated aqueous NH4Cl (20 mL) and 2 mL of 1N HCl
  5. customThe organic phase was collected
  6. extractionthe aqueous phase extracted with EtOAc
  7. washThe combined organic phases were washed with H2O 3 times
  8. customdried
  9. customevaporated
  10. customThe residue was chromatographed

Sources & evidence

ORD record
ord-9359397155bb4c9dbc3fd34480d23ade
Source dataset
uspto-grants-1993_04
Patent number
US05202321

Reaction notes

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