Sodium hydride → 3-Fluoro-4-(3-nitropyridin-4-yloxy)benzenamine

HRID 1670280Notes

Reaction equation

HRID 1670280 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:9]C(=O)CC(NC2C=CC(F)=CC=2)=O)[CH:5]=[CH:6][C:7]=1[OH:8].[H-].[Na+].Cl.Cl[C:27]1[CH:32]=[CH:31][N:30]=[CH:29][C:28]=1[N+:33]([O-:35])=[O:34]>CN(C=O)C.CCOC(C)=O>[F:1][C:2]1[CH:3]=[C:4]([NH2:9])[CH:5]=[CH:6][C:7]=1[O:8][C:27]1[CH:32]=[CH:31][N:30]=[CH:29][C:28]=1[N+:33]([O-:35])=[O:34]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 122442064-Chloro-3-nitropyridine hydrochlorideHCID 44203043N1-(3-Fluoro-4-hydroxyphenyl)-N3-(4-fluorophenyl)malonamide

Product 1

HCID 442030423-Fluoro-4-(3-nitropyridin-4-yloxy)benzenamineYield 60.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To 4-amino-2-fluorophenol (see Step A of Example 19, 127 mg, 1.0 mmol) in DMF (5 mL) at rt under nitrogen was added sodium hydride (80 mg, 2 mmol, 60%). After stirring at rt for 10 min, 4-chloro-3-nitropyridine hydrochloride (Lancaster, 195 mg, 1.0 mmol) was added. The mixture was stirred at rt for 1 h and was then diluted with EtOAc (50 mL) and washed with water, 10% aqueous lithium chloride solution, and then brine (1×30 mL each). The organic layer was dried over anhydrous Na2SO4 and concentrated in vacuo. The crude product was purified by flash column chromatography on silica gel eluting with EtOAc to give the title compound (150 mg, 60%) as a yellow-orange solid. 1H NMR (DMSO-d6) δ 9.13 (s, 1H), 8.63 (d, 1H, J=6 Hz), 7.09 (t, 1H, J=9.2 Hz), 6.92 (d, 1H, J=6 Hz), 6.55 (dd, 1H, J=13.2, 2.4 Hz), 6.45 (dd, 1H, J=9.2, 2.4 Hz), 5.61 (s, 2H); MS (ESI+) m/z 250.18 (M+H)+.

Workup

  1. stirringThe mixture was stirred at rt for 1 h
  2. washwashed with water, 10% aqueous lithium chloride solution
  3. dry with materialThe organic layer was dried over anhydrous Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by flash column chromatography on silica gel eluting with EtOAc

Sources & evidence

ORD record
ord-769532c18ccd44cba61446142256310e
Source dataset
uspto-grants-2011_08
Patent number
US07989477B2

Reaction notes

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