Sodium Iodide → HCID 90408633, compound

Temperature

5 °C

N-(2,5-difluoro-4-(trifluoromethyl)phenyl)acetamide (950 mg, 4.0 mmol) (Prepared according to Y. Tanabe et al, J. Org. Chem. 1988, 53, 4585-4587) was stirred in methanol (25 mL), treated with acetyl chloride (3 mL) and heated at reflux for 2 h. The volatiles were removed by evaporation and the solid residue was dissolved in 6 N HCl (50 mL), cooled to 5° C. and treated in portions with a solution of sodium nitrite (410 mg, 6.0 mmol) in water (5 mL). After 30 min, this mixture was poured into a solution of sodium iodide (2.4 g, 16 mmol) in water (50 mL) and rapidly stirred with dichloromethane (50 mL). After 30 min, solid sodium bisulfate was added to destroy the iodine color, and the separated organic phase was washed with sat. NaCl, dried (Na2SO4), and evaporated. The material was purified by flash chromatography (SiO2, eluting with hexanes) to provide the title compound as a volatile clear liquid (250 mg, 20%): 1H NMR (400 MHz, CDCl3) δ 7.64 (ddd, J=8.8, 4.8, 0.4 Hz, 1H), 7.28 (dd, J=11.1, 4.7 Hz, 1H); 19F NMR (376 MHz, CDCl3) δ −61.92, −97.64, −97.68, −118.59, −118.63, −118.64, −118.67; EIMS m/z 308.

1. temperatureheated
2. temperatureat reflux for 2 h
3. customThe volatiles were removed by evaporation
4. dissolutionthe solid residue was dissolved in 6 N HCl (50 mL)
5. waitAfter 30 min
6. customto destroy the iodine color
7. washthe separated organic phase was washed with sat. NaCl
8. dry with materialdried (Na2SO4)
9. customevaporated
10. customThe material was purified by flash chromatography (SiO2, eluting with hexanes)

ORD record

ord-77df81d8775344ae84cce9cd324add1c

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09113629B2