HCID 12997788, compound → HCID 178441584, compound

HRID 23522Notes

Reaction equation

HRID 23522 reaction equation
[C:1]([C:5]1[N:6](O)[C:7]([C:17]2[CH:22]=[CH:21][NH:20][C:19](=[O:23])[CH:18]=2)=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=2)[N:9]=1)([CH3:4])([CH3:3])[CH3:2]>CO>[C:1]([C:5]1[NH:6][C:7]([C:17]2[CH:22]=[CH:21][NH:20][C:19](=[O:23])[CH:18]=2)=[C:8]([C:10]2[CH:11]=[CH:12][C:13]([F:16])=[CH:14][CH:15]=2)[N:9]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

3

Reactant 1

HCID 12997788HCID 12997788, compound

Product 1

HCID 178441584HCID 178441584, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
10 °C

Procedure

To a solution of 4-[2-tert-butyl-4-(4-fluorophenyl)-1-hydroxy-1H-imidazol-5-yl]pyridin-2(1H)-one (28 g, 0.086 mol) in methanol (1 L) at 0° C. under nitrogen was added TiCl3 (10% w/w in 20% w/w HCl, 450 ml) over 45 minutes while maintaining the reaction temperature under 10° C. The solution was warmed to RT and stirred overnight. The methanol was removed under reduced pressure and the solution was made basic with saturated NaHCO3 and 5 N NaOH. Ethyl acetate was added and it was stirred for 4 hours. The solution was filtered through a Solka floc pad to remove the solids. The filtrate was extracted with EtOAc and the organic layer was then washed twice with brine, dried over Na2SO4 and concentrated to dryness to yield crude product. It was purified by flash chromatography using CH2Cl2/2%-10% methanol as an eluant to yield the title compound as a mixture of imidazole tautomers.

Workup

  1. temperatureThe solution was warmed to RT
  2. customThe methanol was removed under reduced pressure
  3. additionEthyl acetate was added
  4. stirringit was stirred for 4 hours
  5. filtrationThe solution was filtered through a Solka floc pad
  6. customto remove the solids
  7. extractionThe filtrate was extracted with EtOAc
  8. washthe organic layer was then washed twice with brine
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated to dryness
  11. customto yield crude product
  12. customIt was purified by flash chromatography

Sources & evidence

ORD record
ord-940f14fc6b3e48038551d2f6e016abd9
Source dataset
uspto-grants-2005_02
Patent number
US06852727B2

Reaction notes

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