Diisopropylamine → 1-(2,2,2-Trifluoroethyl)-4-((trimethylsilyl)ethynyl)-1H-pyrazole

HRID 2205941Notes

Reaction equation

HRID 2205941 reaction equation
I[C:2]1[CH:3]=[N:4][N:5]([CH2:7][C:8]([F:11])([F:10])[F:9])[CH:6]=1.[Si:12]([C:16]#[CH:17])([CH3:15])([CH3:14])[CH3:13].C(NC(C)C)(C)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CN(C=O)C.[Cu]I>[F:9][C:8]([F:11])([F:10])[CH2:7][N:5]1[CH:6]=[C:2]([C:17]#[C:16][Si:12]([CH3:15])([CH3:14])[CH3:13])[CH:3]=[N:4]1

Participants

7

Reactant 4

HCID 7912DiisopropylamineHCID 11776TriphenylphosphineHCID 66111TrimethylsilylacetyleneHCID 575166204-Iodo-1-(2,2,2-trifluoroethyl)-1H-pyrazole

Product 1

HCID 682905641-(2,2,2-Trifluoroethyl)-4-((trimethylsilyl)ethynyl)-1H-pyrazoleYield 97.6%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

4-Iodo-1-(2,2,2-trifluoroethyl)-1H-pyrazole (Preparation 146, 970 mg, 3.51 mmol) was dissolved in DMF (4.9 mL) and TMS-acetylene (0.7 ml, 486 mg, 4.96 mmol) was added; followed by di-isopropylamine (0.65 mL), copper(I) iodide (44 mg) and triphenylphosphine (184 mg). The reaction was flushed with nitrogen. Palladium acetate (52.5 mg) was added and the reaction flushed again with nitrogen (×3) before heating at 60° C. for 60 minutes. The reaction was cooled and added to water (50 mL). The product was extracted with ether (3×25 mL). The combined organic layers were washed with water (3×20 mL) and brine, then dried (MgSO4) and concentrated in vacuo. The residue was purified using silica gel column chromatography eluting with 1:2 ethyl acetate:cyclohexane to afford the title compound (844 mg, 97%). 1H-NMR (CDCl3, 500 MHz): δ 0.24 (s, 9H), 4.68 (q, J=8.20, 2H), 7.66 (s, 1H), 7.67 (s, 1H).

Workup

  1. customThe reaction was flushed with nitrogen
  2. additionPalladium acetate (52.5 mg) was added
  3. customthe reaction flushed again with nitrogen (×3)
  4. temperatureThe reaction was cooled
  5. additionadded to water (50 mL)
  6. extractionThe product was extracted with ether (3×25 mL)
  7. washThe combined organic layers were washed with water (3×20 mL) and brine
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified
  11. washeluting with 1:2 ethyl acetate

Sources & evidence

ORD record
ord-ffc6a2134f7a4a66892aa7559779ef67
Source dataset
uspto-grants-2016_06
Patent number
US09371319B2

Reaction notes

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