1,1-Dibromoethane → 3-(1-triisopropylsilanyl-1H-indol-5-yl)-azetidine-1-carboxylic acid tert-butyl ester

HRID 1890375Notes

Reaction equation

HRID 1890375 reaction equation
ClC([SiH3])(Cl)Cl.BrC(Br)C.[C:10]([O:14][C:15]([N:17]1[CH2:20][CH:19](I)[CH2:18]1)=[O:16])([CH3:13])([CH3:12])[CH3:11].I[C:23]1[CH:24]=[C:25]2[C:29](=[CH:30][CH:31]=1)[N:28]([Si:32]([CH:39]([CH3:41])[CH3:40])([CH:36]([CH3:38])[CH3:37])[CH:33]([CH3:35])[CH3:34])[CH:27]=[CH:26]2>CC(N(C)C)=O.[Zn].C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Fe].ClCCl.[Cu]I>[C:10]([O:14][C:15]([N:17]1[CH2:20][CH:19]([C:23]2[CH:24]=[C:25]3[C:29](=[CH:30][CH:31]=2)[N:28]([Si:32]([CH:36]([CH3:38])[CH3:37])([CH:39]([CH3:41])[CH3:40])[CH:33]([CH3:34])[CH3:35])[CH:27]=[CH:26]3)[CH2:18]1)=[O:16])([CH3:13])([CH3:12])[CH3:11]

Participants

9

Reactant 4

HCID 112011,1-DibromoethaneHCID 11000522Tert-butyl 3-iodoazetidine-1-carboxylateHCID 685972215-iodo-1-triisopropylsilanyl-1H-indoleHCID 71317501CID 71317501

Product 1

HCID 685963853-(1-triisopropylsilanyl-1H-indol-5-yl)-azetidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 4

HCID 23994ZincCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178478472(1,1'-Bis(diphenylphosphino)ferrocene)dichloropalladium-dichloromethane (1:1)CatalystHCID 31374DimethylacetamideSolvent3×

Conditions

Temperature
65 °C

Procedure

In an inert atmosphere, zinc dust (300 mg, 4.59 mmol) was vigorously stirred in dimethylacetamide (1.6 ml) and heated to 65° C. Subsequently, trichloromethylsilane (70 μl, 0.57 mmol) and dibromoethane (50 μl, 0.57 mmol) were added, and the reaction mixture was stirred for another 30 minutes at 65° C. 3-Iodo-azetidine-1-carboxylic acid tert-butyl ester (1.0 g, 3.53 mmol) in dimethylacetamide (2 ml) was added dropwise to the above prepared solution at 65° C., and then the reaction mixture was allowed to cool to room temperature. 5-Iodo-1-triisopropylsilanyl-1H-indole (855 mg, 1.98 mmol) in dimethylacetamide (4 ml) was added to the reaction mixture. Subsequently, [1,1-bis(diphenylphosphino)ferrocene]dichloropalladium(II)-dichlormethane (52.4 mg, 0.06 mmol) and copper(I)iodide (24.4 mg, 0.13 mmol) were added. The reaction mixture was heated to 80° C. for 2 hours, cooled to room temperature and quenched with water (150 ml). Ammonium chloride (2 g) was added, and the reaction mixture was extracted twice with diethylether (150 ml). The organic layer was dried over magnesium sulphate, filtered, and the solvent was evaporated under reduced pressure to give an oil (1.1 g, 64% purity).

Workup

  1. temperatureto cool to room temperature
  2. temperatureThe reaction mixture was heated to 80° C. for 2 hours
  3. temperaturecooled to room temperature
  4. customquenched with water (150 ml)
  5. additionAmmonium chloride (2 g) was added
  6. extractionthe reaction mixture was extracted twice with diethylether (150 ml)
  7. dry with materialThe organic layer was dried over magnesium sulphate
  8. filtrationfiltered
  9. customthe solvent was evaporated under reduced pressure
  10. customto give an oil (1.1 g, 64% purity)

Sources & evidence

ORD record
ord-c435790127bd4be2a669e7ea7c7511ed
Source dataset
uspto-grants-2013_08
Patent number
US08507469B2

Reaction notes

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