Piperidine → N-(3-methyl-5-trimethylsilanylethynyl-pyridin-2-yl)-2-pyrrolidin-1-yl-acetamide

HRID 1916742Notes

Reaction equation

HRID 1916742 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH3:17])[C:5]([NH:8][C:9](=[O:16])[CH2:10][N:11]2[CH2:15][CH2:14][CH2:13][CH2:12]2)=[N:6][CH:7]=1.[C:18]([Si:20]([CH3:23])([CH3:22])[CH3:21])#[CH:19].N1CCCCC1>C1COCC1.O.[Cu]I>[CH3:17][C:4]1[C:5]([NH:8][C:9](=[O:16])[CH2:10][N:11]2[CH2:15][CH2:14][CH2:13][CH2:12]2)=[N:6][CH:7]=[C:2]([C:19]#[C:18][Si:20]([CH3:23])([CH3:22])[CH3:21])[CH:3]=1

Participants

7

Reactant 3

HCID 8082PiperidineHCID 66111TrimethylsilylacetyleneHCID 67362705N-(5-bromo-3-methyl-pyridin-2-yl)-2-pyrrolidin-1-yl-acetamide

Product 1

HCID 67363112N-(3-methyl-5-trimethylsilanylethynyl-pyridin-2-yl)-2-pyrrolidin-1-yl-acetamide

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Under an argon atmosphere 35 mg (0.03 mmol) tetrakis-triphenylphosphane-palladium and 5.7 mg (0.03 mmol) CuI are added to a solution of 447 mg (1.5 mmol) N-(5-bromo-3-methyl-pyridin-2-yl)-2-pyrrolidin-1-yl-acetamide and 0.23 mL (1.65 mmol) ethynyl-trimethyl-silane in 0.45 mL (4.5 mmol) piperidine and 10 mL THF and the reaction mixture is stirred for 14 h at RT. To complete the reaction a further 35 mg tetrakis-triphenylphosphane-palladium are added and the reaction mixture is heated to 50° C. for 4 h. It is diluted with water, extracted exhaustively with EtOAc, the combined organic phases are washed with saturated NaCl solution and dried over Na2SO4. After the desiccant and solvent have been eliminated the residue is purified by chromatography (silica gel, EtOAc/MeOH/NH3 90:10:1).

Workup

  1. additionare added
  2. temperaturethe reaction mixture is heated to 50° C. for 4 h
  3. extractionextracted exhaustively with EtOAc
  4. washthe combined organic phases are washed with saturated NaCl solution
  5. dry with materialdried over Na2SO4
  6. customis purified by chromatography (silica gel, EtOAc/MeOH/NH3 90:10:1)

Sources & evidence

ORD record
ord-387174d4ac9a41278d9b966b05abf771
Source dataset
uspto-grants-2013_12
Patent number
US08618132B2

Reaction notes

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