Sodium hydride → HCID 23153294, compound

HRID 2069127Notes

Reaction equation

HRID 2069127 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([OH:8])[CH:5]=[CH:4][N:3]=1.[H-].[Na+].F[C:12]1[CH:17]=[CH:16][C:15]([N+:18]([O-:20])=[O:19])=[C:14]([CH3:21])[CH:13]=1>CN(C=O)C.O>[CH3:21][C:14]1[CH:13]=[C:12]([CH:17]=[CH:16][C:15]=1[N+:18]([O-:20])=[O:19])[O:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH2:1])[CH:7]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 949565-Fluoro-2-nitrotolueneHCID 178507942HCID 178507942, compound

Product 1

HCID 23153294HCID 23153294, compoundYield 44.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 2-aminopyridin-4-ol (355 mg, 3.22 mmol) in DMF (4.0 mL) at 0° C. under nitrogen was added portionwise sodium hydride (60% dispersion in mineral oil, 193 mg, 4.83 mmol) and the reaction mixture warmed to RT for 2 hr, The mixture cooled to 0° C. and a solution of 4-fluoro-2-methyl-1-nitrobenzene (500 mg, 3.22 mmol) in DMF (2.0 mL) was added, dropwise and the reaction mixture warmed to RT for 16 hr. The resulting mixture was diluted with water (20 mL) and was extracted with ethyl acetate (3×30 mL). The combined organic extracts were washed with brine (20 mL), then dried (MgSO4) and evaporated in vacuo and the residue was purified by flash column chromatography (SiO2, 40 g, 25% EtOAc in DCM, isocratic elution) to afford 4-(3-methyl-4-nitrophenoxy)pyridin-2-amine as a yellow solid (351 mg, 44%); Rt 1.20 min (Method 2); m/z 246 (M+H)+ (ES+).

Workup

  1. temperatureThe mixture cooled to 0° C.
  2. temperaturedropwise and the reaction mixture warmed to RT for 16 hr
  3. extractionwas extracted with ethyl acetate (3×30 mL)
  4. washThe combined organic extracts were washed with brine (20 mL)
  5. dry with materialdried (MgSO4)
  6. customevaporated in vacuo
  7. customthe residue was purified by flash column chromatography (SiO2, 40 g, 25% EtOAc in DCM, isocratic elution)

Sources & evidence

ORD record
ord-adcdc3cf85bf4fe681dcaee3bbc7883a
Source dataset
uspto-grants-2012_10
Patent number
US08299074B2

Reaction notes

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