1,1-Dibromoethane → 3-(1H-Pyrrolo[2,3-b]pyridin-5-yl)-azetidine-1-carboxylic acid tert-butyl ester

HRID 1890382Notes

Reaction equation

HRID 1890382 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[CH:31]=[CH:30][NH:29][C:26]2=[N:27][CH:28]=1>CC(N(C)C)=O.C(OCC)(=O)C.[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[CH:31]=[CH:30][NH:29][C:26]3=[N:27][CH:28]=2)[CH2:18]1)=[O:16])([CH3:13])([CH3:12])[CH3:11]

Participants

10

Reactant 4

HCID 112011,1-DibromoethaneHCID 11000522Tert-butyl 3-iodoazetidine-1-carboxylateHCID 242292145-Iodo-1H-pyrrolo[2,3-b]pyridineHCID 71317501CID 71317501

Product 1

HCID 685976733-(1H-Pyrrolo[2,3-b]pyridin-5-yl)-azetidine-1-carboxylic acid tert-butyl esterYield 20.1%

Reagents, catalysts & solvents 5

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 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent3×

Conditions

Temperature
65 °C

Procedure

In an inert atmosphere, zinc dust (223 mg, 3.41 mmol) was vigorously stirred in dimethylacetamide (1.5 ml) and heated to 65° C. Subsequently, trichloromethylsilane (50 μl, 0.38 mmol) and dibromoethane (30 μl, 0.38 mmol) were added, and the reaction mixture was stirred for further 30 minutes at 65° C. 3-Iodo-azetidine-1-carboxylic acid tert-butyl ester (462 mg, 1.89 mmol) in dimethylacetamide (2 ml) was added dropwise to the above prepared solution at 65° C. and stirred for 30 minutes. 5-Iodo-1H-pyrrolo[2,3-b]pyridine (697 mg, 2.46 mmol) in dimethylacetamide (4 ml) was added to the reaction mixture. Subsequently, [1,1-bis(diphenylphosphino)ferrocene]dichloropalladium(II)-dichlormethane (93 mg, 0.11 mmol) and copper(I)iodide (108 mg, 0.57 mmol) were added. The reaction mixture was heated to 85° C. for 5 hours, cooled to room temperature, diluted with ethyl acetate and filtered over Celite. The residue was extracted 3 times with water. The organic layer was dried over magnesium sulphate, filtered, and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (EtOAc:cylcohexane) to afford the title compound (104 mg, 20% yield).

Workup

  1. stirringstirred for 30 minutes
  2. temperatureThe reaction mixture was heated to 85° C. for 5 hours
  3. temperaturecooled to room temperature
  4. filtrationfiltered over Celite
  5. extractionThe residue was extracted 3 times with water
  6. dry with materialThe organic layer was dried over magnesium sulphate
  7. filtrationfiltered
  8. customthe solvent was evaporated under reduced pressure
  9. customThe residue was purified by column chromatography on silica gel (EtOAc:cylcohexane)

Sources & evidence

ORD record
ord-fd706ad02735478b8f1441be9b198f25
Source dataset
uspto-grants-2013_08
Patent number
US08507469B2

Reaction notes

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