Ethyl Acetate → 5-Bromo-3-[(trimethylsilyl)ethynyl]pyridin-2-amine

HRID 500726Notes

Reaction equation

HRID 500726 reaction equation
[Br:1][C:2]1[CH:3]=[C:4](I)[C:5]([NH2:8])=[N:6][CH:7]=1.[C:10]([Si:12]([CH3:15])([CH3:14])[CH3:13])#[CH:11].CCOC(C)=O>CCN(CC)CC.[Cu]I.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>[Br:1][C:2]1[CH:3]=[C:4]([C:11]#[C:10][Si:12]([CH3:15])([CH3:14])[CH3:13])[C:5]([NH2:8])=[N:6][CH:7]=1

Participants

7

Reactant 3

HCID 8857Ethyl AcetateHCID 66111TrimethylsilylacetyleneHCID 15165082-Amino-5-bromo-3-iodopyridine

Product 1

HCID 167438055-Bromo-3-[(trimethylsilyl)ethynyl]pyridin-2-amineYield 55.6%

Reagents, catalysts & solvents 3

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

Procedure

To a solution of 5-bromo-3-iodopyridin-2-amine (B-7-1) (20 g, 66.9 mmol) in Et3N (200 mL) was added CuI (1.27 g, 6.69 mmol), and the resulting mixture was degassed with N2 for 2 minutes. Then Pd(PPh3)2Cl2 (1.4 g, 20.1 mmol) was added and the mixture was degassed again. Then ethynyl-trimethyl-silane (7.2 g, 73.6 mmol) was added dropwise into the mixture at 0° C. The mixture was stirred at room temperature for 4 hours. TLC (Petroleum ether: EtOAc=5:1) showed that the reaction was complete. The mixture was evaporated under reduced pressure to give crude mixture which was purified via a silica gel column eluted with petroleum ether/EtOAc (20:1) to afford 5-bromo-3-(2-(trimethylsilyl)ethynyl)pyridin-2-amine (B-7-2) (10 g, 55.6%) as a white solid.

Workup

  1. customthe resulting mixture was degassed with N2 for 2 minutes
  2. customthe mixture was degassed again
  3. customThe mixture was evaporated under reduced pressure
  4. customto give crude mixture which
  5. customwas purified via a silica gel column
  6. washeluted with petroleum ether/EtOAc (20:1)

Sources & evidence

ORD record
ord-edcca135c1924b93b188521d44aa0bd5
Source dataset
uspto-grants-2010_08
Patent number
US07772246B2

Reaction notes

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