1-(Trimethylsilyl)prop-1-yne → 3-Bromo-4-methyl-5-(prop-1-YN-1-YL)pyridine

HRID 539290Notes

Reaction equation

HRID 539290 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Br:9])[C:7]=1[CH3:8].C[Si](C)(C)[C:12]#[C:13][CH3:14].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1(C)C=CC=CC=1.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Br:9][C:6]1[CH:5]=[N:4][CH:3]=[C:2]([C:12]#[C:13][CH3:14])[C:7]=1[CH3:8]

Participants

7

Reactant 3

HCID 803631-(Trimethylsilyl)prop-1-yneHCID 8193383,5-Dibromo-4-methylpyridineHCID 2724141Tetrabutylammonium Fluoride

Product 1

HCID 679795183-Bromo-4-methyl-5-(prop-1-YN-1-YL)pyridineYield 16%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

3,5-Dibromo-4-methylpyridine (0.50 g, 2.0 mmol), 1-(trimethylsilyl)-1-propyne (0.35 mL, 2.4 mmol), copper(I) iodide (0.11 g, 0.60 mmol), tetrakis(triphenylphosphine)palladium(0) (0.023 g, 0.02 mmol) were mixed in toluene (2 mL). The mixture was degassed by a stream of argon for a couple of min. Tetra-n-butylammonium fluoride (1 M in THF) (2.4 mL, 2.4 mmol) was added, and the reaction was heated under N2 at 70° C. overnight. The mixture was partitioned between water containing sat aq. NaHCO3 and EtOAc. The organic phase was dried (MgSO4) and evaporated to give a crude product which was purified by flash chromatography (40 g SiO2, heptane/EtOAc gradient) affording the title compound (0.067 g, 16% yield): 1H NMR (500 MHz, DMSO-d6) δ ppm 2.15 (s, 3 H), 2.46 (s, 3 H), 8.48 (s, 1 H), 8.61 (s, 1 H); MS (ES+) m/z 210 [M+H]+.

Workup

  1. customThe mixture was degassed by a stream of argon for a couple of min
  2. customThe mixture was partitioned between water containing
  3. dry with materialThe organic phase was dried (MgSO4)
  4. customevaporated
  5. customto give a crude product which
  6. customwas purified by flash chromatography (40 g SiO2, heptane/EtOAc gradient)

Sources & evidence

ORD record
ord-0a23d9a0a6744524b70b047aaa5388f4
Source dataset
uspto-grants-2014_10
Patent number
US08865911B2

Reaction notes

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