2,6-Lutidine → 5-(Benzyloxy)-1-(phenylsulfonyl)-1H-indole-4-carbaldehyde

HRID 2423116Notes

Reaction equation

HRID 2423116 reaction equation
Br[C:2]1[C:10]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][N:6]2[S:19]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)(=[O:21])=[O:20].C(C([Sn])=C(CCCC)CCCC)CCC.N1C(C)=CC=CC=1C.I([O-])(=O)(=O)=O.[Na+].[O:57]1CCOC[CH2:58]1>C1(C)C=CC=CC=1.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O=[Os](=O)(=O)=O>[CH2:12]([O:11][C:10]1[CH:9]=[CH:8][C:7]2[N:6]([S:19]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)(=[O:21])=[O:20])[CH:5]=[CH:4][C:3]=2[C:2]=1[CH:58]=[O:57])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

10

Reactant 5

HCID 79372,6-LutidineHCID 312751,4-Dioxane2×HCID 23667635Sodium periodateHCID 53438229Tri(butyl)vinyltinHCID 67240891HCID 67240891, compound2×

Product 1

HCID 866182505-(Benzyloxy)-1-(phenylsulfonyl)-1H-indole-4-carbaldehyde

Reagents, catalysts & solvents 4

HCID 30318Osmium TetroxideCatalystHCID 178418476HCID 178418476, compoundCatalyst2×HCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

To a warm solution of 4-bromo-5-benzyloxy-1-(phenylsulfonyl)-1H-indole (Intermediate 3, 4.74 g, 10.7 mmol) in toluene (100 mL) was added tributylvinyltin (6.80 g, 21.4 mmol) and Pd(PPh3)2Cl2 (0.37 g, 0.50 mmol). The solution was heated at reflux for two hours and more Pd(PPh3)2Cl2 (0.20 g, 0.30 mmol) was added and the reaction mixture was refluxed overnight. A teaspoon of silica gel was added and the mixture was filtered through a pad of silica gel. The solvent was removed under reduced pressure and the resulting oil was triturated with petroleum ether to give a semicrystalline mass (3.6 g) that was dissolved in dioxane (110 mL) and 2,6-lutidine (2.00 g, 18.7 mmol) and OsO4 (0.24 g, 0.94 mmol) were added. The mixture was stirred at room temperature for five minutes. To the dark solution was added a solution of sodium periodate (8.02 g, 37.5 mmol) in water (35 mL) and the resulting suspension was stirred for 30 minutes. More dioxane (40 mL) was added and the mixture was filtered. The filtrate was evaporated to give a dark red oil. The crude product was purified by flash chromatography on silica gel using petroleum ether/EtOAc 90:10 followed by 80:20 as eluent to give the title compound (2.44 g) as a yellow solid. MS m/z 392 [M+H]+.

Workup

  1. temperatureThe solution was heated
  2. temperatureat reflux for two hours
  3. temperaturethe reaction mixture was refluxed overnight
  4. additionA teaspoon of silica gel was added
  5. filtrationthe mixture was filtered through a pad of silica gel
  6. customThe solvent was removed under reduced pressure
  7. customthe resulting oil was triturated with petroleum ether
  8. customto give a semicrystalline mass (3.6 g) that
  9. stirringthe resulting suspension was stirred for 30 minutes
  10. filtrationthe mixture was filtered
  11. customThe filtrate was evaporated
  12. customto give a dark red oil
  13. customThe crude product was purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-fa01a6276d934b79916361bab09e829c
Source dataset
uspto-grants-2011_06
Patent number
US07960374B2

Reaction notes

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