2,6-Lutidine → HCID 86644333, compound

HRID 1877998Notes

Reaction equation

HRID 1877998 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[NH:10][C:9](=[O:11])[O:8][C:7]([CH2:16]O)([C:12]([F:15])([F:14])[F:13])[C:6]=2[CH:18]=1.CC1C=CC=C(C)N=1.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.C(=O)([O-])O.[Na+].[N-:47]=[N+:48]=[N-:49].[Na+]>C(Cl)(Cl)Cl.C1COCC1.C(OCC)(=O)C.O>[N:47]([CH2:16][C:7]1([C:12]([F:15])([F:14])[F:13])[C:6]2[CH:18]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=2[NH:10][C:9](=[O:11])[O:8]1)=[N+:48]=[N-:49]

Participants

10

Reactant 5

HCID 79372,6-LutidineHCID 33557Sodium AzideHCID 67749Trifluoromethanesulfonic anhydrideHCID 516892Sodium BicarbonateHCID 68488597HCID 68488597, compound

Product 1

HCID 86644333HCID 86644333, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

6-Chloro-4-(hydroxymethyl)-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-2-one (4.0 g, 14.2 mmol) was dissolved in chloroform (30 mL) and THF (15 mL), and while stirring the mixture at 0° C., 2,6-dimethylpyridine (13.2 mL, 113 mmol) and trifluoromethanesulfonic anhydride (9.6 mL, 56.8 mmol) were sequentially added thereto. After the reaction solution was stirred for 3 hours under ice-cooling, a saturated aqueous sodium hydrogen carbonate solution was added thereto under ice-cooling. Then, the solution was diluted with ethyl acetate and the organic layer was separated. The organic layer was washed sequentially with a 10% aqueous citric acid solution and saturated brine and then dried over magnesium sulfate. After the drying agent was removed by filtration, the solvent was evaporated under reduced pressure. The resulting residue was dissolved in DMF (50 mL), and sodium azide (1.53 g, 23.5 mmol) was added thereto. After the reaction solution was stirred overnight at 80° C., the temperature of the solution was brought to room temperature and water was added thereto. The solution was diluted with ethyl acetate and the organic layer was separated. The organic layer was washed with saturated brine and then dried over magnesium sulfate. After the drying agent was removed by filtration, the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane=1/2), whereby the objective compound (3.47 g, 80%) was obtained as a white solid.

Workup

  1. temperaturecooling
  2. temperatureunder ice-cooling
  3. customthe organic layer was separated
  4. washThe organic layer was washed sequentially with a 10% aqueous citric acid solution and saturated brine
  5. dry with materialdried over magnesium sulfate
  6. customAfter the drying agent was removed by filtration
  7. customthe solvent was evaporated under reduced pressure
  8. dissolutionThe resulting residue was dissolved in DMF (50 mL)
  9. stirringAfter the reaction solution was stirred overnight at 80° C.
  10. customwas brought to room temperature
  11. customthe organic layer was separated
  12. washThe organic layer was washed with saturated brine
  13. dry with materialdried over magnesium sulfate
  14. customAfter the drying agent was removed by filtration
  15. customthe solvent was evaporated under reduced pressure
  16. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane=1/2), whereby the objective compound (3.47 g, 80%)
  17. customwas obtained as a white solid

Sources & evidence

ORD record
ord-bb3261bcedd6434bb62ba116132ccf5a
Source dataset
uspto-grants-2012_11
Patent number
US08314094B2

Reaction notes

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