Sodium hydride → 3-(2-Bromo-4-(trifluoromethyl)phenoxy)pyridin-2-amine

HRID 1806131Notes

Reaction equation

HRID 1806131 reaction equation
[NH2:1][C:2]1[C:7]([OH:8])=[CH:6][CH:5]=[CH:4][N:3]=1.[H-].[Na+].[Br:11][C:12]1[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[CH:14][C:13]=1F>CN(C=O)C>[Br:11][C:12]1[CH:17]=[C:16]([C:18]([F:19])([F:20])[F:21])[CH:15]=[CH:14][C:13]=1[O:8][C:7]1[C:2]([NH2:1])=[N:3][CH:4]=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 24758Sodium hydride2×HCID 281142-Amino-3-HydroxypyridineHCID 1442953-Bromo-4-fluorobenzotrifluoride

Product 1

HCID 669947023-(2-Bromo-4-(trifluoromethyl)phenoxy)pyridin-2-amine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 2-aminopyridin-3-ol (1.00 g, 9.08 mmol) and DMF (20 mL) was cooled in a 0° C. bath and sodium hydride (0.240 g, 9.49 mmol) was slowly added in portions with vigorous stirring (significant gas evolution). After the addition was completed, the mixture was stirred at ambient temperature for 30 minutes to ensure all the NaH was consumed (reaction becomes very viscous). The 2-bromo-1-fluoro-4-(trifluoromethyl)benzene (1.17 mL, 8.26 mmol) was added and the mixture heated to 110° C. under nitrogen overnight. The reaction was cooled to ambient temperature and the DMF removed under reduced pressure. The resulting black sludge was quenched with 0.5 N NaOH (100 mL) and extracted with Et2O). The organic layer was washed with 1N NaOH and brine, dried over sodium sulfate, filtered and concentrated to afford a brown solid. The solids were purified on silica gel eluting with 40% EtOAc/Hexanes to afford 3-(2-bromo-4-(trifluoromethyl)phenoxy)pyridin-2-amine the title compound.

Workup

  1. additionAfter the addition
  2. stirringthe mixture was stirred at ambient temperature for 30 minutes
  3. customwas consumed
  4. custom(reaction becomes very viscous)
  5. temperaturethe mixture heated to 110° C. under nitrogen overnight
  6. temperatureThe reaction was cooled to ambient temperature
  7. customthe DMF removed under reduced pressure
  8. customThe resulting black sludge was quenched with 0.5 N NaOH (100 mL)
  9. extractionextracted with Et2O)
  10. washThe organic layer was washed with 1N NaOH and brine
  11. dry with materialdried over sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customto afford a brown solid
  15. customThe solids were purified on silica gel eluting with 40% EtOAc/Hexanes

Sources & evidence

ORD record
ord-4b4ccd8c1d39413e8ea67e633c005739
Source dataset
uspto-grants-2013_01
Patent number
US08354540B2

Reaction notes

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