Phenol → HCID 18760197, compound

HRID 432689Notes

Reaction equation

HRID 432689 reaction equation
[H-].[Na+].[C:3]1([OH:9])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Cl[C:11]1[C:20]2[N:21]=[CH:22][N:23]([CH2:24][CH2:25][O:26][CH2:27][C:28]#[CH:29])[C:19]=2[C:18]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[N:12]=1.[O-]C1C=CC=CC=1.[Na+]>COCCOCCOC>[O:9]([C:11]1[C:20]2[N:21]=[CH:22][N:23]([CH2:24][CH2:25][O:26][CH2:27][C:28]#[CH:29])[C:19]=2[C:18]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[N:12]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1

Participants

6

Reactant 4

HCID 996PhenolHCID 24758Sodium hydrideHCID 4445035Phenolate SodiumHCID 18760200HCID 18760200, compound

Product 1

HCID 18760197HCID 18760197, compoundYield 44.6%

Reagents, catalysts & solvents 1

HCID 8150DiglymeSolvent2×

Conditions

Temperature
110 °C

Procedure

A dried round bottom flask was charged with a stir bar, sodium hydride (8.15 g, 203.9 mmol) and anhydrous 2-methoxylethyl ether (diglyme, 100 mL) while under a nitrogen atmosphere and at ambient temperature. Phenol (20.7 g, 220.2 mmol) was added in several portions as a solid and the resulting solution stirred under a nitrogen atmosphere until gas evolution ceased. 4-chloro-1-[2-(prop-2-ynyloxy)ethyl]-1H-imidazo[4,5-c]quinoline (46.6 g, 163.1 mmol) was added neat and the solution was heated to 110° C. After 15.5 hours, a preformed solution of sodium phenoxide (phenol 5 g, 53.1 mmol and sodium hydride 1.91 g, 47.8 mmol) in diglyme (20 mL) was added to the reaction solution and heating was increased to 165° C. The reaction was judged complete after 1 hour at 165° C. After cooling to less than 70° C., the volatiles were removed under reduced pressure and the resulting brown solid was partitioned between chloroform and saturated aqueous sodium carbonate. The aqueous fraction was extracted with chloroform; the combined organic fractions were dried with anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure to provide a brown solid. The solid was recrystallized from acetonitrile with a small amount of dimethyl formamide to provide 25 g of 4-phenoxy-1-[2-(prop-2-ynyloxy)ethyl]-1H-imidazo[4,5-c]quinoline as a crystalline solid.

Workup

  1. additionA dried round bottom flask was charged with a stir bar
  2. customat ambient temperature
  3. temperatureheating
  4. temperaturewas increased to 165° C
  5. waitThe reaction was judged complete after 1 hour at 165° C
  6. temperatureAfter cooling to less than 70° C.
  7. customthe volatiles were removed under reduced pressure
  8. customthe resulting brown solid was partitioned between chloroform and saturated aqueous sodium carbonate
  9. extractionThe aqueous fraction was extracted with chloroform
  10. dry with materialthe combined organic fractions were dried with anhydrous magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customto provide a brown solid
  14. customThe solid was recrystallized from acetonitrile with a small amount of dimethyl formamide

Sources & evidence

ORD record
ord-9c23a4fa38954d98a769652badec3f2e
Source dataset
uspto-grants-2003_12
Patent number
US06664260B2

Reaction notes

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