Ethylene Glycol → 2-[2-(tert-Butyl-dimethyl-silanyloxy)-ethoxy]-4-iodo-pyridine

HRID 419150Notes

Reaction equation

HRID 419150 reaction equation
F[C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][N:3]=1.[CH2:9]([OH:12])[CH2:10][OH:11].[H-].[Na+].[C:15]([Si:19](Cl)([CH3:21])[CH3:20])([CH3:18])([CH3:17])[CH3:16].C(N(CC)CC)C>O.CN(C=O)C>[C:15]([Si:19]([CH3:21])([CH3:20])[O:11][CH2:10][CH2:9][O:12][C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][N:3]=1)([CH3:18])([CH3:17])[CH3:16]

Participants

8

Reactant 5

HCID 174Ethylene GlycolHCID 8471TriethylamineHCID 24758Sodium hydrideHCID 28928tert-Butyldimethylsilyl chlorideHCID 70235702-Fluoro-4-iodopyridine

Product 1

HCID 579424932-[2-(tert-Butyl-dimethyl-silanyloxy)-ethoxy]-4-iodo-pyridineYield 61.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

2-Fluoro-4-iodo-pyridine (607 mg, 2.72 mmol), ethylene glycol (760 uL, 13.6 mmol) and 60% sodium hydride (120 mg, 2.99 mmol) were sequentially added to 2 mL of anhydrous DMF at room temperature. The solution was then brought to 60° C. and stirred for 2 hours, then cooled down and diluted with 20 mL of water. The mixture was extracted 2 times with 30 mL of diethyl ether. The combined organic layers were washed with 10 mL of water, then 10 mL of brine and dried over anhydrous magnesium sulfate. After concentrating the mixture under reduced pressure, the residue was dissolved in 2 mL of anhydrous acetonitrile. To this solution tert-butylchlorodimethylsilane (453 mg, 3.00 mmol) and triethylamine (459 μL, 3.30 mmol) were added and the mixture was stirred at r.t. for 3 days following evaporation under reduced pressure. The residue was taken up in 40 mL of a 1:1 mixture of diethyl ether and water. The organic layer was concentrated under reduced pressure and the residue purified on a 40 g silica column eluted with a gradient of 0-15% ethyl acetate in hexanes to yield 630 mg of the product as colorless oil. MS: (M+H)/z=380.0.

Workup

  1. customwas then brought to 60° C.
  2. temperaturecooled down
  3. extractionThe mixture was extracted 2 times with 30 mL of diethyl ether
  4. washThe combined organic layers were washed with 10 mL of water
  5. dry with material10 mL of brine and dried over anhydrous magnesium sulfate
  6. concentrationAfter concentrating the mixture under reduced pressure
  7. dissolutionthe residue was dissolved in 2 mL of anhydrous acetonitrile
  8. stirringthe mixture was stirred at r.t. for 3 days
  9. customevaporation under reduced pressure
  10. additionThe residue was taken up in 40 mL of a 1:1 mixture of diethyl ether and water
  11. concentrationThe organic layer was concentrated under reduced pressure
  12. customthe residue purified on a 40 g silica column
  13. washeluted with a gradient of 0-15% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-5df223c0bd9a4a3da580f0bc6b61fb27
Source dataset
uspto-grants-2012_01
Patent number
US08093247B2

Reaction notes

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