Sodium hydride → 1-[2,6,7-Trimethyl-4-phenoxy-1H-imidazo[4,5-c]pyridin-1-yl]eth-2-yl [(2E)-3-Phenylprop-2-enyl]Ether

HRID 1008010Notes

Reaction equation

HRID 1008010 reaction equation
[H-].[Na+].[CH3:3][C:4]1[N:5]([CH2:22][CH2:23][OH:24])[C:6]2[C:11]([CH3:12])=[C:10]([CH3:13])[N:9]=[C:8]([O:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:7]=2[N:21]=1.[CH2:25](Br)[CH:26]=[CH:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>CN(C)C=O.C(Br)C=CC1C=CC=CC=1>[CH3:3][C:4]1[N:5]([CH2:22][CH2:23][O:24][CH2:25]/[CH:26]=[CH:27]/[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:6]2[C:11]([CH3:12])=[C:10]([CH3:13])[N:9]=[C:8]([O:14][C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:7]=2[N:21]=1

Participants

6

Reactant 3

HCID 24758Sodium hydride3×HCID 98116BromomethylstyreneHCID 219131391-[2,6,7-Trimethyl-4-phenoxy-1H-imidazo[4,5-c]pyridin-1-yl]ethan-2-ol

Product 1

HCID 219129941-[2,6,7-Trimethyl-4-phenoxy-1H-imidazo[4,5-c]pyridin-1-yl]eth-2-yl [(2E)-3-Phenylprop-2-enyl]EtherYield 71.9%

Reagents, catalysts & solvents 2

HCID 98116BromomethylstyreneCatalystHCID 6228DimethylformamideSolvent3×

Procedure

Sodium hydride (0.41 g, 10.24 mmol, 60% in mineral oil) and anhydrous N,N-dimethylformamide (10 mL) were combined and stirred for 5 minutes under nitrogen. A solution of 1-[2,6,7-trimethyl-4-phenoxy-1H-imidazo[4,5-c]pyridin-1-yl]ethan-2-ol (2.9 g, 9.752 mmol) from Part G of Example 7 in N,N-dimethylformamide (15 mL) was then added to the sodium hydride over 5 minutes. After stirring the resulting reaction solution for 10 minutes at room temperature, a solution of cinnamyl bromide (2.11 g, 10.73 mmol) in N,N-dimethylformamide (15 mL) was added to the reaction solution, and the resulting reaction mixture was stirred for 4 hours and 10 minutes. Sodium hydride (0.10 g, 60% in mineral oil) and then cinnamyl bromide (0.1 g) were added to the reaction mixture, and after stirring for 30 minutes, HPLC monitoring of the reaction mixture indicated about 9% starting material remaining. The reaction mixture was concentrated under reduced pressure, and the resulting oil was dissolved in dichloromethane. The dichloromethane solution was washed with saturated ammonium chloride (3×), water (3×), and brine (3×), dried with magnesium sulfate, filtered, and concentrated under reduced pressure to a white solid, which contained about 6% starting material by HPLC analysis. The white solid was passed through a column of silica (120 g, 40×200 mm) using 95/5 ethyl acetate/dichloromethane. The isolated product was triturated with diethyl ether, filtered off, and dried to provide 2.9 g of product with no starting material. This was carried on to the next step.

Workup

  1. stirringAfter stirring
  2. customthe resulting reaction solution for 10 minutes at room temperature
  3. customthe resulting reaction mixture
  4. stirringwas stirred for 4 hours and 10 minutes
  5. stirringafter stirring for 30 minutes
  6. concentrationThe reaction mixture was concentrated under reduced pressure
  7. dissolutionthe resulting oil was dissolved in dichloromethane
  8. washThe dichloromethane solution was washed with saturated ammonium chloride (3×), water (3×), and brine (3×)
  9. dry with materialdried with magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure to a white solid, which
  12. customThe isolated product was triturated with diethyl ether
  13. filtrationfiltered off
  14. customdried

Sources & evidence

ORD record
ord-c3e6c0125a40433cbd234ae366a286cc
Source dataset
uspto-grants-2004_09
Patent number
US06797718B2

Reaction notes

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