Water → 4-(2-Methoxy-4-nitrophenoxy)pyridin-2-amine

HRID 2069130Notes

Reaction equation

HRID 2069130 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([OH:8])[CH:5]=[CH:4][N:3]=1.C1CCN2C(=NCCC2)CC1.F[C:21]1[CH:26]=[CH:25][C:24]([N+:27]([O-:29])=[O:28])=[CH:23][C:22]=1[O:30][CH3:31].O>CC#N.CN(C=O)C>[CH3:31][O:30][C:22]1[CH:23]=[C:24]([N+:27]([O-:29])=[O:28])[CH:25]=[CH:26][C:21]=1[O:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH2:1])[CH:7]=1

Participants

7

Reactant 4

HCID 962WaterHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 144519681-Fluoro-2-methoxy-4-nitrobenzeneHCID 178507942HCID 178507942, compound

Product 1

HCID 585648114-(2-Methoxy-4-nitrophenoxy)pyridin-2-amineYield 51.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Procedure

To a suspension of 2-aminopyridin-4-ol (0.251 g, 2.28 mmol) in MeCN (4.0 mL) at RT was added DBU (423 μl, 2.80 mmol) and after 30 min a solution of 1-fluoro-2-methoxy-4-nitrobenzene (300 mg, 1.75 mmol) in DMF (2.0 mL) was added dropwise. The reaction mixture was maintained at RT for 1 hr and was then heated to 80° C. for 16 hr. After cooling to RT water (2.0 mL) was added and the mixture was evaporated in vacuo. The residue was partitioned between DCM (30 mL) and brine (20 mL) and the organic layer was separated and dried (MgSO4) and was evaporated in vacuo. The residue was purified by flash column chromatography (SiO2, 40 g, EtOAc in isohexane, 20-100%, gradient elution) to afford 4-(2-methoxy-4-nitrophenoxy)pyridin-2-amine as a bright yellow solid (234 mg, 50%); Rt 1.25 min (Method 2); m/z 262 (M+H)+ (ES+).

Workup

  1. temperaturewas then heated to 80° C. for 16 hr
  2. additionwas added
  3. customthe mixture was evaporated in vacuo
  4. customThe residue was partitioned between DCM (30 mL) and brine (20 mL)
  5. customthe organic layer was separated
  6. dry with materialdried (MgSO4)
  7. customwas evaporated in vacuo
  8. customThe residue was purified by flash column chromatography (SiO2, 40 g, EtOAc in isohexane, 20-100%, gradient elution)

Sources & evidence

ORD record
ord-53622d9faf94499e90eb09adf2f5676d
Source dataset
uspto-grants-2012_10
Patent number
US08299074B2

Reaction notes

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