1,2,3,5-Tetrafluoro-4-nitrobenzene → 2,3,5-trifluoro-N-(2-fluoro-4-iodophenyl)-6-nitroaniline

A solution of 4-iodo-2-fluoro aniline (3.64 g, 15.37 mmol) in dry THF (100 mL) was cooled to −78° C. in a dry ice-acetone bath under a nitrogen atmosphere. To this solution was added dropwise via syringe a 1 M solution of LHDMS in THF (15.4 mL). During the addition the solution turns green and the mixture was stirred at that temperature for an additional 1 h. The mixture was cooled and to it was then added dropwise a solution of 1,2,3,5-tetrafluoro-4-nitrobenzene (3 g, 15.37 mmol) in dry THF (10.0 mL) via syringe. During the addition the color of the mixture changes to dark purple. The mixture was then allowed to stir at −78° C. for 1 h and then warmed to room temperature and stirred overnight (12 h). The mixture was then concentrated under vacuo to remove ⅔ of the THF, diluted with ethyl acetate (100 mL), washed with water (2×50 mL), and finally with brine. The organic layer was dried over MgSO4 and evaporated under reduced pressure. The crude material was purified by careful flash column chromatography over silica gel using a 1-5% ethyl acetate/hexanes gradient to afford the desired product as a yellow solid (4.4 g, 70%). 1H NMR (400 MHz, DMSO-d6): 6.85 (t, 1H), 7.35 (d, 1H), 7.60-7.65 (m, 2H), 8.78 (s, 1H).

1. additionDuring the addition the solution
2. temperatureThe mixture was cooled and to it
3. additionDuring the addition the color of the mixture changes to dark purple
4. stirringto stir at −78° C. for 1 h
5. stirringstirred overnight (12 h)
6. concentrationThe mixture was then concentrated under vacuo
7. customto remove ⅔ of the THF
8. additiondiluted with ethyl acetate (100 mL)
9. washwashed with water (2×50 mL)
10. dry with materialThe organic layer was dried over MgSO4
11. customevaporated under reduced pressure
12. customThe crude material was purified by careful flash column chromatography over silica gel using a 1-5% ethyl acetate/hexanes gradient

ORD record

ord-402944fb2f664335ae9d3bf6163ccc76

Source dataset

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09034861B2