Chlorotrimethylsilane → HCID 59351395, compound

HRID 887434Notes

Reaction equation

HRID 887434 reaction equation
Cl[Si](C)(C)C.BrCCBr.I[CH:11]1[CH2:17][CH2:16][CH2:15][O:14][CH2:13][CH2:12]1.[F:18][C:19]1[C:24](I)=[N:23][CH:22]=[CH:21][N:20]=1>CC(N(C)C)=O.[Zn].[Cu]I>[F:18][C:19]1[C:24]([CH:11]2[CH2:17][CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)=[N:23][CH:22]=[CH:21][N:20]=1

Participants

8

Reactant 4

HCID 6397ChlorotrimethylsilaneHCID 78391,2-DibromoethaneHCID 153696932-Fluoro-3-iodopyrazineHCID 59351387HCID 59351387, compound

Product 1

HCID 59351395HCID 59351395, compound

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 31374DimethylacetamideSolvent3×

Procedure

A mixture of chlorotrimethylsilane (0.11 mL, 0.87 mmol) and 1,2 dibromoethane (0.075 mL, 0.87 mmol) was added slowly to a stirred mixture of zinc dust (0.71 g, 10.9 mmol) in DMA (2 mL) at room temperature under a nitrogen atmosphere. The mixture was stirred for 15 min before a solution of 4-iodooxepane (1.97 g, 8.71 mmol) in DMA (5 mL) was added dropwise via syringe. The reaction mixture was stirred at room temperature for an additional 30 min before being warmed to 60° C. for 15 min. The reaction mixture was cooled to room temperature and added directly via syringe to a stirred mixture of 2-fluoro-3-iodopyrazine (1.39 g, 6.23 mmol), copper(i) iodide (0.12 g, 0.62 mmol), and dichloro(1,1-bis(diphenylphosphinoferrocene))palladium(ii) (0.25 g, 0.31 mmol) in DMA (8 mL) under an argon atmosphere. The reaction mixture was stirred at 80° C. for 3 h. The reaction mixture was cooled to room temperature, quenched with sat. ammonium chloride, and extracted with EtOAc. The organic layer was separated, washed with sat. sodium chloride, dried over magnesium sulfate, filtered, and concentrated in vacuo. The resulting crude product was purified by silica gel chromatography to give 2-fluoro-3-(oxepan-4-yl)pyrazine. [M+1]=197.1.

Workup

  1. additionwas added dropwise via syringe
  2. temperaturebefore being warmed to 60° C. for 15 min
  3. temperatureThe reaction mixture was cooled to room temperature
  4. stirringThe reaction mixture was stirred at 80° C. for 3 h
  5. temperatureThe reaction mixture was cooled to room temperature
  6. customquenched with sat. ammonium chloride
  7. extractionextracted with EtOAc
  8. customThe organic layer was separated
  9. washwashed with sat. sodium chloride
  10. dry with materialdried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customThe resulting crude product was purified by silica gel chromatography

Sources & evidence

ORD record
ord-9bd09c734fd045858e9449b173396e5b
Source dataset
uspto-grants-2012_08
Patent number
US08247418B2

Reaction notes

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