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

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Reaction Steps

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).

Provenance & Evidence