Tetrahydrofuran → 7-(2-trifluoromethyl-phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine

HRID 1943692Notes

Reaction equation

HRID 1943692 reaction equation
O1CCCC1.Br[C:7]1[CH:16]=[N:15][C:10]2[O:11][CH2:12][CH2:13][NH:14][C:9]=2[CH:8]=1.[F:17][C:18]([F:29])([F:28])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1B(O)O.C(=O)([O-])[O-].[K+].[K+]>O>[F:17][C:18]([F:29])([F:28])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[C:7]1[CH:16]=[N:15][C:10]2[O:11][CH2:12][CH2:13][NH:14][C:9]=2[CH:8]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 11430Potassium CarbonateHCID 27343872-(Trifluoromethyl)benzeneboronic acidHCID 667890617-bromo-1H,2H,3H-pyrido[2,3-b][1,4]oxazine

Product 1

HCID 669363367-(2-trifluoromethyl-phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazineYield 64.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To 3 ml of tetrahydrofuran/0.5 ml of distilled water, 7-bromo-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine (80.0 mg, 0.37 mmol), 2-trifluoromethyl-phenyl boronic acid (78 mg, 0.41 mmol), potassium carbonate (103 mg, 0.74 mmol) and tetrakis triphenylphosphine palladium (21 mg, 0.02 mmol) were added and then stirred at 800 for 2 hours. After completion of the reaction, the mixture was extracted with ethyl acetate, and the combined organic layer was dried over anhydrous sodium sulfate (Na2SO4), filtered and evaporated under reduced pressure. The residue was purified by column chromatography on amine silica eluting with a solvent of dichloromethane:methanol=50:1. The fractions containing the product were collected and evaporated to obtain 7-(2-trifluoromethyl-phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine as white solid (67 mg, 64%).

Workup

  1. customAfter completion of the reaction
  2. extractionthe mixture was extracted with ethyl acetate
  3. dry with materialthe combined organic layer was dried over anhydrous sodium sulfate (Na2SO4)
  4. filtrationfiltered
  5. customevaporated under reduced pressure
  6. customThe residue was purified by column chromatography on amine silica eluting with a solvent of dichloromethane
  7. additionThe fractions containing the product
  8. customwere collected
  9. customevaporated

Sources & evidence

ORD record
ord-719bc71f89da4f4ca43cc9f5f0bd3353
Source dataset
uspto-grants-2013_03
Patent number
US08394792B2

Reaction notes

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