Phenol → Phenyl 2-{4-[(4,6-dimethyl-3-nitro-2-pyridinyl)amino]phenyl}ethylcarbamate

HRID 724114Notes

Reaction equation

HRID 724114 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([CH2:16][CH2:17]C(O)=O)=[CH:12][CH:11]=2)[C:3]=1[N+:21]([O-:23])=[O:22].C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:31])C=CC=CC=1.C([N:43]([CH2:46]C)CC)C.[C:48]1([OH:54])[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1>O1CCOCC1>[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]([NH:9][C:10]2[CH:11]=[CH:12][C:13]([CH2:16][CH2:17][NH:43][C:46](=[O:31])[O:54][C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)=[CH:14][CH:15]=2)[C:3]=1[N+:21]([O-:23])=[O:22]

Participants

6

Reactant 4

HCID 996Phenol2×HCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 218756763-{4-[(4,6-Dimethyl-3-nitro-2-pyridinyl)amino]phenyl]propanoic acid

Product 1

HCID 21875604Phenyl 2-{4-[(4,6-dimethyl-3-nitro-2-pyridinyl)amino]phenyl}ethylcarbamateYield 79.9%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

To a stirred solution of 3-{4-[(4,6-dimethyl-3-nitro-2-pyridinyl)amino]phenyl}propanoic acid (step 1, 10 g, 31.7 mmol) in dioxane (200 mL) was added diphenylphosphoryl azide (DPPA) (7.54 ml, 35 mmol) and triethylamine (4.87 mL, 35 mmol). The reaction mixture was heated at 120° C. for 2 h. To the reaction mixture was added phenol (6.6 g, 70 mmol) and the reaction mixture was refluxed. After 3 h, to the reaction mixture was added an additional amount of phenol (3.3 g, 35 mmol). The resulting mixture was heated under reflux temperature overnight. The volatile component was removed and the residue was partitioned between aqueous 10% aqueous citric acid (200 mL) and ethyl acetate (300 mL). The organic phase was separated and the aqueous phase was extracted with ethyl acetate (300 mL). The combined organic extracts were washed with water (300 mL) and brine (300 mL), then dried (Na2SO4), and concentrated. The crude product was purified by flash column chromatography on silica gel eluting with hexane/EtOAc (2:1) to afford 10.3 g (77%) of the title compound as orange solids.

Workup

  1. temperaturethe reaction mixture was refluxed
  2. temperatureThe resulting mixture was heated
  3. temperatureunder reflux temperature overnight
  4. customThe volatile component was removed
  5. customthe residue was partitioned between aqueous 10% aqueous citric acid (200 mL) and ethyl acetate (300 mL)
  6. customThe organic phase was separated
  7. extractionthe aqueous phase was extracted with ethyl acetate (300 mL)
  8. washThe combined organic extracts were washed with water (300 mL) and brine (300 mL)
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated
  11. customThe crude product was purified by flash column chromatography on silica gel eluting with hexane/EtOAc (2:1)

Sources & evidence

ORD record
ord-993191aec17a41acb99c565bba2f0dc9
Source dataset
uspto-grants-2006_11
Patent number
US07141580B2

Reaction notes

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