Trimethylsilylacetylene → 5-(Trifluoromethyl)-3-((trimethylsilyl)ethynyl)-pyridin-2-amine

HRID 1515910Notes

Reaction equation

HRID 1515910 reaction equation
I[C:2]1[C:3]([NH2:12])=[N:4][CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[CH3:13][Si:14]([C:17]#[CH:18])([CH3:16])[CH3:15]>C(N(CC)CC)C.O1CCCC1.[Cu]I.C1(P([Pd-](Cl)P(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:9][C:8]([F:11])([F:10])[C:6]1[CH:7]=[C:2]([C:18]#[C:17][Si:14]([CH3:16])([CH3:15])[CH3:13])[C:3]([NH2:12])=[N:4][CH:5]=1

Participants

7

Reactant 2

HCID 66111TrimethylsilylacetyleneHCID 153509143-Iodo-5-(trifluoromethyl)pyridin-2-amine

Product 1

HCID 467368715-(Trifluoromethyl)-3-((trimethylsilyl)ethynyl)-pyridin-2-amineYield 94.2%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178479804HCID 178479804, compoundCatalystHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

3-Iodo-5-trifluoromethyl-pyridin-2-ylamine (52.5 g, 180 mmol) was dissolved in a mixture of triethylamine (76 mL) and tetrahydrofuran (300 mL) and the solution was degassed and purged with nitrogen. Trimethylsilyl acetylene (38 mL, 270 mmol), copper(I) iodide (0.7 g, 3.6 mmol) and bis(triphenylphosphino) palladium (II) chloride (2.53 g, 3.6 mmol) were added. The mixture was degassed and purged with nitrogen one more time. The mixture was stirred at ambient temperature for 16 h and a solution containing a white precipitate resulted. The precipitate was removed by filtration, and the filtrate was concentrated in vacuo. The residue was purified by flash column chromatography (silica gel from QingDao, 200-300 mesh, 15%-35% ethyl acetate in hexanes) to afford 5-trifluoromethyl-3-trimethylsilanylethynyl-pyridin-2-ylamine (43.8 g, 92%) as a yellow solid: LC/MS m/e calcd for C11H13F3N2Si [M+H]+ 259.32, observed 258.9.

Workup

  1. customthe solution was degassed
  2. custompurged with nitrogen
  3. customThe mixture was degassed
  4. custompurged with nitrogen one more time
  5. additiona solution containing a white precipitate
  6. customresulted
  7. customThe precipitate was removed by filtration
  8. concentrationthe filtrate was concentrated in vacuo
  9. customThe residue was purified by flash column chromatography (silica gel from QingDao, 200-300 mesh, 15%-35% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-59f9d2a4b5ef4e5db9d7132f8036db58
Source dataset
uspto-grants-2012_07
Patent number
US08222416B2

Reaction notes

Loading…