Urea → 2-Tert-butyl-5-nitrophenol

Temperature

2.5 °C

To a mixture of 2-tert-butyl-5-nitroaniline (1.94 g, 10 mmol) in 40 mL of 15% H2SO4 was added dropwise a solution of NaNO2 (763 mg, 11.0 mmol) in water (3 mL) at 0° C. The resulting mixture was stirred at 0-5° C. for 5 min. Excess NaNO2 was neutralized with urea, then 5 mL of H2SO4—H2O (v/v 1:2) was added and the mixture was refluxed for 5 min. Three additional 5 mL aliquots of H2SO4—H2O (v/v 1:2) were added while heating at reflux. The reaction mixture was cooled to room temperature and extracted with EtOAc twice. The combined organic layers were washed with brine and dried over MgSO4. After removal of solvent, the residue was purified by column chromatography (0-10% EtOAc—Hexane) to give 2-tert-butyl-5-nitrophenol (C-1-a) (1.2 g, 62%). 1H NMR (400 MHz, CDCl3) δ 7.76 (dd, J=8.6, 2.2 Hz, 1H), 7.58 (d, J=2.1 Hz, 1H), 7.43 (d, J=8.6 Hz, 1H), 5.41 (s, 1H), 1.45 (s, 9H); HPLC ret. time 3.46 min, 10-99% CH3CN, 5 min run.

1. temperaturethe mixture was refluxed for 5 min
2. temperaturewhile heating
3. temperatureat reflux
4. temperatureThe reaction mixture was cooled to room temperature
5. extractionextracted with EtOAc twice
6. washThe combined organic layers were washed with brine
7. dry with materialdried over MgSO4
8. customAfter removal of solvent
9. customthe residue was purified by column chromatography (0-10% EtOAc—Hexane)

ORD record

ord-44b5a1827f82440bb8e1d4b4c4996bd7

Source dataset

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08629162B2