Trimethylsilylacetylene → HCID 90403368, compound

HRID 1049269Notes

Reaction equation

HRID 1049269 reaction equation
Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[C:10]([CH3:18])=[N:11][C:12]([N+:15]([O-:17])=[O:16])=[CH:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1.C[Si]([C:23]#[CH:24])(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>CN(C=O)C.CCOC(C)=O.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:23]([C:2]1[CH:7]=[C:6]([O:8][C:9]2[C:10]([CH3:18])=[N:11][C:12]([N+:15]([O-:17])=[O:16])=[CH:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1)#[CH:24]

Participants

8

Reactant 3

HCID 66111TrimethylsilylacetyleneHCID 2724141Tetrabutylammonium FluorideHCID 904036213-((2-Chloropyridin-4-yl)oxy)-2-methyl-6-nitropyridine

Product 1

HCID 90403368HCID 90403368, compoundYield 10.6%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

To a degassed solution of Example A4 (5.0 g, 18.8 mmol) in DMF (30 mL) was added TEA (7.87 mL, 56.5 mmol), Pd(PPh3)2Cl2 (0.661 g, 0.941 mmol), copper(I) iodide (0.179 g, 0.941 mmol), and trimethylsilylacetylene (7.9 mL, 56 mmol) and the mixture was stirred at 50° C. for 16 h. The mixture was diluted with EtOAc (60 mL) and filtered through diatomaceous earth, washing the pad with EtOAc (5×10 mL). The combined filtrates were concentrated to a volume of ˜20 mL, treated with a solution of TBAF (1M in THF, 38 mL, 38 mmol), and stirred at RT for 3 h. The mixture was partitioned between EtOAc (200 mL) and water (200 mL) and stirred for a few minutes. The resultant emulsion was filtered through diatomaceous earth, washing with water (2×20 mL) and EtOAc (3×20 mL). The filtrate layers were separated and the aqueous layer was extracted with EtOAc (50 mL). The combined organics were washed with brine, dried (Na2SO4) and concentrated. The residue was purified by silica gel chromatography (EtOAc/Hex) to afford 3-((2-ethynylpyridin-4-yl)oxy)-2-methyl-6-nitropyridine (0.51 g, 10.6%) as a light brown solid. MS (ESI) m/z: 256.1 (M+H+).

Workup

  1. filtrationfiltered through diatomaceous earth
  2. washwashing the pad with EtOAc (5×10 mL)
  3. concentrationThe combined filtrates were concentrated to a volume of ˜20 mL
  4. stirringstirred at RT for 3 h
  5. customThe mixture was partitioned between EtOAc (200 mL) and water (200 mL)
  6. stirringstirred for a few minutes
  7. filtrationThe resultant emulsion was filtered through diatomaceous earth
  8. washwashing with water (2×20 mL) and EtOAc (3×20 mL)
  9. customThe filtrate layers were separated
  10. extractionthe aqueous layer was extracted with EtOAc (50 mL)
  11. washThe combined organics were washed with brine
  12. dry with materialdried (Na2SO4)
  13. concentrationconcentrated
  14. customThe residue was purified by silica gel chromatography (EtOAc/Hex)

Sources & evidence

ORD record
ord-e721ea52bebf49ee9ac1c8b1be33ba23
Source dataset
uspto-grants-2016_07
Patent number
US09382228B2

Reaction notes

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