2-Iodo-4,5-Difluoroaniline

Colorless Liquid

3, 4-Difluoroaniline (645mg, 5mmol) was suspended in water (25 mL). Sodium bicarbonate (630 mg, 7.5 mmol) was added and then iodine (1.65 g, 6.5 mmol). The reaction mixture was stirred vigorously at ambient temperature for 30min and then poured into saturated sodium thiosulphate solution (50 mL) and extracted with ethyl acetate (2x25 mL). The combined extracts were washed with sodium thiosulphate (20 mL), water (20 mL) and brine (20 mL), dried (MgSOAt room temperature, a solution of 3, 4-difluoroaniline (100 μL, 1 mmol) and N-iodosuccinimide (225 mg, 1 mmol) in anhydrous dichloromethane (4 mL) was stirred overnight under argon atmosphere. Then an aqueous solution of sodium sulfite was added and the reaction mixture was extracted with dichloromethane. The combined organic extracts were dried over sodium sulfate, filtered and evaporated. The crude product was purified by flash chromatography (silica gel, cyclohexane/ethyl acetate, 1/0 to 8/2) to afford 4, 5-difluoro-2-iodoaniline (175 mg, 69percent) as a red oil. ESI-MS m/z 255.9 (M+H)Reference Example 3a 2-methyl-5, 6-fluoro-2, 3-dihydro-1H-indole Step 1a:4, 5-Difluoro-2-iodoaniline 16.5 g of iodine and 6.3 g of sodium bicarbonate are added, at ambient temperature, to a suspension of 6.45 g of 3, 4-difluoroaniline in 250 ml of water. The reaction medium is stirred at ambient temperature for 1 hour.A saturated sodium thiosulfate solution is added and then the resulting mixture is extracted 3 times with ethyl acetate. The organic phases are combined, dried over magnesium sulfate, filtered, and then concentrated under reduced pressure, so as to give 12 g of 4, 5-difluoro-2-iodoainiline, the characteristics of which are the following:Mass spectrometry: method ARetention time Tr (min)=0.90; [M+H]+: m/z 256; base peak: m/z 2973, 4-Difluoroaniline (645mg, 5mmol) was suspended in water (25 mL). Sodium bicarbonate (630 mg, 7.5 mmol) was added and then iodine (1.65 g, 6.5 mmol). The reaction mixture was stirred vigorously at ambient temperature for 30min and then poured into saturated sodium thiosulphate solution (50 mL) and extracted with ethyl acetate (2x25 mL). The combined extracts were washed with sodium thiosulphate (20 mL), water (20 mL) and brine (20 mL), dried (MgSOAt room temperature, a solution of 3, 4-difluoroaniline (100 μL, 1 mmol) and N-iodosuccinimide (225 mg, 1 mmol) in anhydrous dichloromethane (4 mL) was stirred overnight under argon atmosphere. Then an aqueous solution of sodium sulfite was added and the reaction mixture was extracted with dichloromethane. The combined organic extracts were dried over sodium sulfate, filtered and evaporated. The crude product was purified by flash chromatography (silica gel, cyclohexane/ethyl acetate, 1/0 to 8/2) to afford 4, 5-difluoro-2-iodoaniline (175 mg, 69percent) as a red oil. ESI-MS m/z 255.9 (M+H)Reference Example 3a 2-methyl-5, 6-fluoro-2, 3-dihydro-1H-indole Step 1a:4, 5-Difluoro-2-iodoaniline 16.5 g of iodine and 6.3 g of sodium bicarbonate are added, at ambient temperature, to a suspension of 6.45 g of 3, 4-difluoroaniline in 250 ml of water. The reaction medium is stirred at ambient temperature for 1 hour.A saturated sodium thiosulfate solution is added and then the resulting mixture is extracted 3 times with ethyl acetate. The organic phases are combined, dried over magnesium sulfate, filtered, and then concentrated under reduced pressure, so as to give 12 g of 4, 5-difluoro-2-iodoainiline, the characteristics of which are the following:Mass spectrometry: method ARetention time Tr (min)=0.90; [M+H]+: m/z 256; base peak: m/z 297

Molecular Weight:255.00
XLogP3:2.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Exact Mass:254.93565
Monoisotopic Mass:254.93565
Topological Polar Surface Area:26
Heavy Atom Count:10
Complexity:122
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes