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

Temperature

120 °C

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.

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)

ORD record

ord-78e4d3ab314e4987a53c3d6d3e73a7f0

Source dataset

uspto-grants-2006_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07148234B2