Water → 8-Bromo-2-(difluoromethoxy)-6-methylquinoxaline

HRID 1781238Notes

Reaction equation

HRID 1781238 reaction equation
[OH-].[Na+].[Br:3][C:4]1[CH:5]=[C:6]([CH3:15])[CH:7]=[C:8]2[C:13]=1[N:12]=[C:11]([OH:14])[CH:10]=[N:9]2.Cl[CH:17]([F:19])[F:18].O>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O1CCOCC1>[Br:3][C:4]1[CH:5]=[C:6]([CH3:15])[CH:7]=[C:8]2[C:13]=1[N:12]=[C:11]([O:14][CH:17]([F:19])[F:18])[CH:10]=[N:9]2

Participants

7

Reactant 4

HCID 962WaterHCID 6372ChlorodifluoromethaneHCID 14798Sodium HydroxideHCID 178422420HCID 178422420, compound

Product 1

HCID 152390158-Bromo-2-(difluoromethoxy)-6-methylquinoxalineYield 52%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 312751,4-DioxaneSolvent

Procedure

Tetrabutylammonium bromide (689 mg, 2.14 mmol) and sodium hydroxide (17.1 g of a 50% aqueous solution, 214 mmol) were added to a solution of the title compound of Step D (5.11 g, 21.4 mmol) in dioxane (250 mL) at room temperature. Chlorodifluoromethane was condensed with a cold finger trap and added to the reaction mixture until the mixture was saturated. The reaction mixture was allowed to stir at room temperature overnight. The reaction mixture was slowly poured into water. The resulting mixture was extracted with ethyl acetate three times. The combined organic extracts were dried (MgSO4), filtered, and concentrated under reduced pressure to give a dark-brown oil. Flash chromatography of this brown oil on silica gel, eluting with 1:25 ethyl acetate/hexane afforded the title compound of Step E as a light yellow solid melting at 86°-87° C. (3.23 g, 52%). 1H NMR (CDCl3): δ2.57 (s,3H), 7.75 (t, 1H), 7.84 (s, 1H), 7.92 (s, 1H), 8.58 (s, 1H).

Workup

  1. customcondensed with a cold finger trap
  2. additionadded to the reaction mixture until the mixture
  3. extractionThe resulting mixture was extracted with ethyl acetate three times
  4. dry with materialThe combined organic extracts were dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto give a dark-brown oil
  8. washFlash chromatography of this brown oil on silica gel, eluting with 1:25 ethyl acetate/hexane

Sources & evidence

ORD record
ord-aa24d111c02e4dc5a5481afc71f24fef
Source dataset
uspto-grants-1997_05
Patent number
US05633218

Reaction notes

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