Water → 4-(Difluoromethoxy)-2-iodoaniline
Reaction equation
[F:1][CH:2]([F:11])[O:3][C:4]1[CH:10]=[CH:9][C:7]([NH2:8])=[CH:6][CH:5]=1.[I:12]Cl.O>CC(O)=O>[I:12][C:9]1[CH:10]=[C:4]([O:3][CH:2]([F:11])[F:1])[CH:5]=[CH:6][C:7]=1[NH2:8]Participants
5
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 85 °C
Procedure
A solution of 4-(difluoromethoxy)aniline (1.0 g, 6.30 mmol) in AcOH (6 mL) was heated to 60° C. and iodine monochloride (1.07 g, 6.6 mmol) in AcOH (15 mL) was added dropwise. The reaction mixture was then heated to 85° C. and stirred for 1.5 h. The reaction mixture was cooled to r.t. and poured into cold water and the resulting suspension filtered. The filtrate was concentrated in vacuo to give a dark brown oil. Purification by column chromatography (SiO2, 10-20% EtOAc/hexanes) gave the title compound (0.40 g, 22%) as a dark brown oil. δH (DMSO-d6) 7.38 (1H, d, J 2.7 Hz), 6.98-6.94 (1H, m), 6.97 (1H, t, J 74.8 Hz), 6.75 (1H, d, J 8.8 Hz), 5.20 (2H, br. s). LCMS (ES+) 286.0 (M+H)+, RT 3.28 minutes (Method 5).
Workup
- temperatureThe reaction mixture was cooled to r.t.
- filtrationthe resulting suspension filtered
- concentrationThe filtrate was concentrated in vacuo
- customto give a dark brown oil
- customPurification by column chromatography (SiO2, 10-20% EtOAc/hexanes)
Sources & evidence
- ORD record
- ord-cd7aabcc4d83491db1ba314a01f2e99e
- Source dataset
- uspto-grants-2012_08
- Patent number
- US08242116B2
Reaction notes
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