N-Boc-4-hydroxyaniline → tert-Butyl 4-(2-(methylamino)-3-nitropyridin-4-yl-oxy)phenylcarbamate

HRID 1864671Notes

Reaction equation

HRID 1864671 reaction equation
[C:1]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CC(C)([O-])C.[K+].Cl[C:23]1[CH:28]=[CH:27][N:26]=[C:25]([NH:29][CH3:30])[C:24]=1[N+:31]([O-:33])=[O:32]>CN(C=O)C>[CH3:30][NH:29][C:25]1[C:24]([N+:31]([O-:33])=[O:32])=[C:23]([O:15][C:12]2[CH:11]=[CH:10][C:9]([NH:8][C:1](=[O:2])[O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[CH:14][CH:13]=2)[CH:28]=[CH:27][N:26]=1

Participants

5

Reactant 3

HCID 2756771N-Boc-4-hydroxyanilineHCID 23665647Potassium tert-butoxideHCID 249031234-Chloro-N-methyl-3-nitropyridin-2-amine

Product 1

HCID 42625417tert-Butyl 4-(2-(methylamino)-3-nitropyridin-4-yl-oxy)phenylcarbamateYield 60%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

N-Boc-4-hydroxyaniline (334 mg, 1.6 mmol) was dissolved in dry DMF (5 mL) and the solution was degassed by argon bubbling for 10 minutes. Potassium tert-butoxide (179 mg, 1.6 mmol) was added, and the stirring and argon bubbling continued for 50 minutes. 4-Chloro-N-methyl-3-nitropyridin-2-amine (260 mg, 1.4 mmol) was added to the reaction mixture. The reaction mixture was heated and stirred at 80° C. for 9 hours, under argon. The solvent was evaporated and the residue was extracted between DCM and aqueous NaOH 1M. The extraction was repeated twice, the organic layer was dried over MgSO4, and evaporated. The residue was purified by column chromatography (eluent gradient DCM to DCM:AcOEt 15:1) to afford the title compound (300 mg, 60%). 1H-NMR (δ, ppm, DMSO-d6): 1.48 (s, 9H, t-Bu), 2.91 (d, 3H, Me, J=4.60 Hz), 5.94 (d, 1H, HPy,5, J=5.70 Hz), 7.09 (d, 2H, Harom,Ph,3+5, J=9.00 Hz), 7.45 (m, 1H, NHPy), 7.53 (d, 2H, Harom,Ph,2+6), 8.07 (d, 1H, HPy,6), 9.46 (s, 1H, NH).

Workup

  1. customthe solution was degassed by argon bubbling for 10 minutes
  2. temperatureThe reaction mixture was heated
  3. customThe solvent was evaporated
  4. extractionthe residue was extracted between DCM and aqueous NaOH 1M
  5. extractionThe extraction
  6. dry with materialthe organic layer was dried over MgSO4
  7. customevaporated
  8. customThe residue was purified by column chromatography (eluent gradient DCM to DCM:AcOEt 15:1)

Sources & evidence

ORD record
ord-4e3e0c42a6fb4c2e8dc509ade7274c1c
Source dataset
uspto-grants-2009_12
Patent number
US07625922B2

Reaction notes

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