Triethylamine → 5-Bromo-2-[(tert-butyldimethylsilanyl)ethynyl]-3-fluoropyridine

HRID 734798Notes

Reaction equation

HRID 734798 reaction equation
[C:1]([Si:5]([C:8]#[CH:9])([CH3:7])[CH3:6])([CH3:4])([CH3:3])[CH3:2].Br[C:11]1[C:16]([F:17])=[CH:15][C:14]([Br:18])=[CH:13][N:12]=1.C(N(CC)CC)C>C1COCC1.[Cu]I>[Br:18][C:14]1[CH:15]=[C:16]([F:17])[C:11]([C:9]#[C:8][Si:5]([C:1]([CH3:4])([CH3:3])[CH3:2])([CH3:7])[CH3:6])=[N:12][CH:13]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 2757281(tert-Butyldimethylsilyl)acetylene2×HCID 224128322,5-Dibromo-3-fluoropyridine

Product 1

HCID 690610065-Bromo-2-[(tert-butyldimethylsilanyl)ethynyl]-3-fluoropyridine

Reagents, catalysts & solvents 2

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

Procedure

Under an argon atmosphere, 2.62 mL (13.811 mmol) of tert-butylethynyldimethylsilane was added to a solution of 3.20 g (12.56 mmol) of 2,5-dibromo-3-fluoropyridine, 5.22 mL of triethylamine (37.67 mmol), 59.8 mg (0.31 mmol) of CuI, and 220.3 mg (0.31 mmol) of bis(triphenylphosphane)palladium (II) chloride in 30 mL of absolute THF at 15° C. and the mixture was stirred for 2 hours at RT. 1 mL of tert-butylethynyldimethylsilane was added and the mixture was again stirred for 1 hour at RT. The reaction mixture was evaporated down in vacuo and the residue was taken up in EtOAc. The organic phase was washed with semisaturated aqueous sodium bicarbonate solution, 5% aqueous ammonia, and water, dried over magnesium sulfate, and evaporated down in vacuo. The crude product was purified by column chromatography (silica gel, PE/DCM 9:1). Yield: 1.62 g (41% of theoretical); C13H17BrFNSi (M=314.269); calc.: molpeak (M+H)+: 314/316 (Br); found: molpeak (M+H)+: 314/316 (Br); HPLC-MS: 7.85 minutes (method B).

Workup

  1. stirringthe mixture was again stirred for 1 hour at RT
  2. customThe reaction mixture was evaporated down in vacuo
  3. washThe organic phase was washed with semisaturated aqueous sodium bicarbonate solution, 5% aqueous ammonia, and water
  4. dry with materialdried over magnesium sulfate
  5. customevaporated down in vacuo
  6. customThe crude product was purified by column chromatography (silica gel, PE/DCM 9:1)
  7. custom7.85 minutes (method B)

Sources & evidence

ORD record
ord-8bc5682cbceb4b2b9629f78812d60c0a
Source dataset
uspto-grants-2009_09
Patent number
US07592358B2

Reaction notes

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