Water → 1-(2-Amino-5-bromophenyl)-2,2,2-trifluoroethanone

Participants

Reaction Steps

A solution of 1-(5-bromo-2-fluorophenyl)-2,2,2-trifluoroethanone (6.67 g, 24.6 mmol, Intermediate 7, step a) in DMSO (6.2 mL) was treated with NaN3 (1.76 g, 27.0 mmol) and stirred under air (lightly capped) at 95° C. for 1 hour. The brownish-red opaque reaction was then cooled to room temperature on an ice bath, diluted with EtOAc (49 mL), treated with SnCl2.dihydrate (6.66 g, 29.5 mmol) in several portions over ˜30 seconds followed by water (1.33 mL, 73.8 mmol), and the mixture was stirred at room temperature for 30 minutes. The reddish solution with heavy off-white particulates was then treated with anhydrous Na2SO4 (˜6 g) and stirred vigorously for a few minutes. The mixture was then filtered over a bed of Celite®, and the cloudy orange filtrate was dry load flash chromatographed (˜60 g silica gel) with a heptane to 50% DCM/heptane gradient to provide the title compound as an orange oil that crystallized upon standing.

Provenance & Evidence