Reaction #74677

Reaction equation

iodine

chloroform

3-fluoro-4-(trifluoromethyl)phenol

chloroform

→

product

Yield 55.7%

5-Fluoro-2-iodo-4-(trifluoromethyl)phenol

Yield 55.7%

Conditions

Workup

1. 1
   workup.ADDITIONAfter addition
2. 2
   FiltrationThe reaction mixture was filtered through diatomaceous earth
3. 3
   Washthe filtrate was washed successively with 10% aqueous sodium thiosulfate (w/v), half-saturated aqueous sodium bicarbonate, water and brine
4. 4
   DryingThe organic phase was dried over sodium sulfate
5. 5
   Filtrationfiltered
6. 6
   Concentrationconcentrated onto diatomaceous earth
7. 7
   OtherThe residue was purified by automated flash chromatography (24 g SiO2, hexanes to 1:1 methylene chloride-hexanes gradient elution)
8. 8
   workup.ADDITIONThe initial product-containing fraction
9. 9
   ConcentrationThe remaining fractions were concentrated in vacuo

Procedure

A solution of iodine (0.874 g, 3.44 mmol) in chloroform (17.1 mL, 214 mmol) was added over a period of 1.5 hours dropwise via addition funnel to a mixture of 3-fluoro-4-(trifluoromethyl)phenol (Preparation 886, 620 mg, 3.4 mmol) and silver trifluoroacetate (0.760 g, 3.44 mmol) in chloroform (3.4 mL, 43 mmol). After addition was complete, the reaction mixture was stirred an additional 1 hour. The reaction mixture was filtered through diatomaceous earth, and the filtrate was washed successively with 10% aqueous sodium thiosulfate (w/v), half-saturated aqueous sodium bicarbonate, water and brine. The organic phase was dried over sodium sulfate, filtered, and concentrated onto diatomaceous earth. The residue was purified by automated flash chromatography (24 g SiO2, hexanes to 1:1 methylene chloride-hexanes gradient elution). The initial product-containing fraction contained predominantly diiodinated material (by mass) with some monoiododinated material. The remaining fractions were concentrated in vacuo to afford the product as a light yellow oil (579 mg, 54%). The product was not dried under vacuum due to volatility.

Source