Sodium hydride → 4-(2-Chloropyridin-4-yloxy)-3-fluorobenzenamine
Reaction equation
[H-].[Na+].[F:3][C:4]1[CH:9]=[C:8]([NH2:10])[CH:7]=[CH:6][C:5]=1[OH:11].[Cl:12][C:13]1[CH:18]=[C:17]([N+]([O-])=O)[CH:16]=[CH:15][N:14]=1>CN(C=O)C>[Cl:12][C:13]1[CH:18]=[C:17]([O:11][C:5]2[CH:6]=[CH:7][C:8]([NH2:10])=[CH:9][C:4]=2[F:3])[CH:16]=[CH:15][N:14]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 90 °C
Procedure
Sodium hydride (60%, 0.104 g, 2.60 mmol, 1.1 eq) was added to a solution of 2-fluoro-4-aminophenol (0.30 g, 2.36 mmol, 1.0 eq) in DMF (6.5 mL) at room temperature and the reaction mixture was stirred for 30 minutes. 2-Chloro-4-nitropyridine (Aldrich, 0.374 g, 2.36 mmol, 1.0 eq) was added and the reaction mixture was heated to 90° C. for 12 h. The reaction mixture was cooled to room temperature, quenched with saturated aqueous NaCl solution and extracted with ethyl acetate (3×70 mL). The combined organic extracts were washed with 10% aq. LiCl solution (3×70 mL), dried over Na2SO4, filtered and the filtrate concentrated in vacuo to afford the title compound (0.430 g, 76%) which was used without further purification. 1H NMR (DMSO-d6) δ 8.27 (d, 1H, J=5.7 Hz), 6.90-7.04 (m, 3H), 6.42-6.54 (m, 2H), 5.54 (s, 2H); MS (ESI+) m/z 239 (M+H)+; HRMS (ESI+) calcd.: 239.0387. found: 239.0391.
Workup
- temperatureThe reaction mixture was cooled to room temperature
- customquenched with saturated aqueous NaCl solution
- extractionextracted with ethyl acetate (3×70 mL)
- washThe combined organic extracts were washed with 10% aq. LiCl solution (3×70 mL)
- dry with materialdried over Na2SO4
- filtrationfiltered
- concentrationthe filtrate concentrated in vacuo
Sources & evidence
- ORD record
- ord-5f4c8f7cb15b497c823b3a5940ae1d2d
- Source dataset
- uspto-grants-2011_08
- Patent number
- US07989477B2
Reaction notes
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