Dimethylformamide → Ethyl 2-(3-((trimethylsilyl)ethynyl)pyrazin-2-yl)acetate

HRID 1473120Notes

Reaction equation

HRID 1473120 reaction equation
Cl[C:2]1[C:3]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])=[N:4][CH:5]=[CH:6][N:7]=1.CN(C=O)C.[CH3:19][Si:20]([C:23]#[CH:24])([CH3:22])[CH3:21]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.C(N(CC)CC)C>[CH3:19][Si:20]([C:23]#[C:24][C:2]1[C:3]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])=[N:4][CH:5]=[CH:6][N:7]=1)([CH3:22])[CH3:21]

Participants

7

Reactant 3

HCID 6228DimethylformamideHCID 66111TrimethylsilylacetyleneHCID 53419385Ethyl 2-(3-chloropyrazin-2-yl)acetate

Product 1

HCID 68282873Ethyl 2-(3-((trimethylsilyl)ethynyl)pyrazin-2-yl)acetateYield 72%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8471TriethylamineSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of the ethyl 2-(3-chloropyrazin-2-yl)acetate (I99) (0.410 g, 2.04 mmol), DMF (6 mL), triethylamine (2 mL), bis(triphenylphosphine)palladium(II) chloride (72 mg, 5 mol %) and copper(I) iodide (19 mg, 5 mol %) in a Schlenk tube was degassed with three vacuum/nitrogen cycles, then trimethylsilylacetylene (0.866 mL, 6.13 mmol) was added under nitrogen. The tube was flushed with nitrogen, sealed and heated to 90° C. After 18 hours the mixture was cooled and poured into water (50 mL). Saturated ammonium chloride (50 mL) was added, and the mixture was extracted with diethyl ether (3×100 mL). The combined ether phases were washed with brine, dried (sodium sulphate) and evaporated. The residue was chromatographed (40 g silica cartridge, 0-30% ethyl acetate/petroleum benzine 40-60° C.) to give the title compound (I100) (0.386 g, 72% yield) as a yellow oil; 1H NMR (400 MHz, CDCl3) δ 8.47-8.41 (m, 2H), 4.20 (q, J=7.1 Hz, 2H), 4.05 (s, 2H), 1.26 (t, J=7.1 Hz), 0.28 (s, 9H). LCMS Method C: rt 6.20 min; m/z 263.1 [M+H]+.

Workup

  1. customwas degassed with three vacuum/nitrogen cycles
  2. customThe tube was flushed with nitrogen
  3. customsealed
  4. temperatureAfter 18 hours the mixture was cooled
  5. additionpoured into water (50 mL)
  6. additionSaturated ammonium chloride (50 mL) was added
  7. extractionthe mixture was extracted with diethyl ether (3×100 mL)
  8. washThe combined ether phases were washed with brine
  9. dry with materialdried (sodium sulphate)
  10. customevaporated
  11. customThe residue was chromatographed (40 g silica cartridge, 0-30% ethyl acetate/petroleum benzine 40-60° C.)

Sources & evidence

ORD record
ord-b745b2b92b09402faf9d7e680f5c6a8b
Source dataset
uspto-grants-2015_04
Patent number
US09012461B2

Reaction notes

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