2-Bromopyridine → HCID 10494836, compound

HRID 326592Notes

Reaction equation

HRID 326592 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[CH2:8]([Li])[CH2:9][CH2:10]C.[C:13]([C:15]1[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[CH:17][C:16]=1[OH:25])#[N:14]>O1CCCC1.CCCCCC>[F:24][C:21]([F:22])([F:23])[C:19]1[CH:18]=[CH:17][C:16]2[O:25][C:9]([CH3:10])([CH3:8])[N:14]=[C:13]([C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=3)[C:15]=2[CH:20]=1

Participants

6

Reactant 3

HCID 79732-BromopyridineHCID 107262312-Hydroxy-5-trifluoromethylbenzonitrileHCID 178418339Butyllithium

Product 1

HCID 10494836HCID 10494836, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

A solution of 2-bromopyridine (0.47 g) in anhydrous tetrahydrofuran (5 ml) was cooled to -78° C. and 1.6M n-butyllithium in hexane (2.1 ml) was added dropwise under an argon atmosphere. The mixture was stirred for 30 minutes. Then, a solution of 2-cyano-4-trifluoromethylphenol (0.19 g) in anhydrous tetrahydrofuran (5 ml) was added to the reaction mixture and the resulting mixture was stirred at -78° C. for an additional 1 hour. The reaction was quenched by adding acetic acid (0.18 g) to the reaction mixture and the solvent was distilled off under reduced pressure. Ammonium acetate (2 g) and 2,2-dimethoxypropane (5 ml) were added to the residue and the mixture was heated under reflux for 3 hours. The solvent was distilled off and the residue was extracted by addition of ethyl acetate and aqueous sodium bicarbonate solution. The ethyl acetate layer was washed with saturated saline solution and dried over anhydrous magnesium sulfate and the solvent was distilled off. The residue was purified by column chromatography on silica gel to obtain 6-trifluoromethyl-2,2-dimethyl-4-(2-pyridyl)-2H-1,3-benzoxazine (0.19 g) (Compound 74).

Workup

  1. stirringthe resulting mixture was stirred at -78° C. for an additional 1 hour
  2. customThe reaction was quenched
  3. additionby adding acetic acid (0.18 g) to the reaction mixture
  4. distillationthe solvent was distilled off under reduced pressure
  5. additionAmmonium acetate (2 g) and 2,2-dimethoxypropane (5 ml) were added to the residue
  6. temperaturethe mixture was heated
  7. temperatureunder reflux for 3 hours
  8. distillationThe solvent was distilled off
  9. extractionthe residue was extracted by addition of ethyl acetate and aqueous sodium bicarbonate solution
  10. washThe ethyl acetate layer was washed with saturated saline solution
  11. dry with materialdried over anhydrous magnesium sulfate
  12. distillationthe solvent was distilled off
  13. customThe residue was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-edca1f213ff54e41871cef777e512b5a
Source dataset
uspto-grants-1993_12
Patent number
US05270308

Reaction notes

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