Reaction #45341

Reaction equation

NaHSO3

t-butyl nitrite

3-methoxy-5-(trifluoromethyl)aniline

Iodine

→

1-iodo-3-methoxy-5-(trifluoromethyl)benzene

Solvents

CHCl3

Conditions

Workup

1. 1
   Temperaturewas maintained at this temperature for an hour and thirty minutes
2. 2
   TemperatureThe reaction was then cooled to room temperature
3. 3
   ExtractionThe mixture was extracted with EtOAc (50 mL)
4. 4
   Washthe organic extracts were washed with aq. NaHSO3 (3×50 mL) and brine (20 mL)
5. 5
   Dryingdried over Na2SO4
6. 6
   Filtrationfiltered
7. 7
   Concentrationconcentrated
8. 8
   OtherPurification by flash chromatography with 1% to 15% EtOAc/hexanes

Procedure

3-methoxy-5-(trifluoromethyl)aniline (100 mg, 0.52 mmol) was dissolved in CHCl3 (5.2 mL) and t-butyl nitrite (124 μL, 1.05 mmol) was added dropwise by syringe. Iodine (266 mg, 1.05 mmol) was added and then the reaction was slowly heated to 50° C. and was maintained at this temperature for an hour and thirty minutes. The reaction was then cooled to room temperature and poured into aq. NaHSO3 (50 mL). The mixture was extracted with EtOAc (50 mL) and the organic extracts were washed with aq. NaHSO3 (3×50 mL) and brine (20 mL), dried over Na2SO4, filtered, and concentrated. Purification by flash chromatography with 1% to 15% EtOAc/hexanes afforded 1-iodo-3-methoxy-5-(trifluoromethyl)benzene. Rf=0.75 (25% EtOAc/hexanes). 1H NMR (CDCl3, 500 MHz) δ 7.53 (s, 1H), 7.41 (s, 1H), 7.09 (s, 1H), 3.82 (s, 3H).

Source