Synthesis
Step A. Preparation of 2-chloro-4-nitro-1-trifluoromethylbenzene
1-bromo-2-chloro-4-nitrobenzene (1.86 g, 7.86 mmol) and CuI (0.225 g, 1.18 mmol) were mixed in
anhydrous DMF (50 mL) were mixed and degassed with N2 for 15 min. Methyl fluorosulfonyl difluoroacetate (3.53 g, 23.6 mmol) was added and the mixture was heated at 80 C for 16 hours. After cooling to room temperature, the reaction mixture was partitioned between ethyl acetate (100 mL) and brine (100 mL). The aqueous layer was extracted with additional ethyl acetate (100 mL). The combined organics were washed with 3 x 200 mL of brine, dried with Na2sO4, concentrated and purified by chromatography, eluting with ethyl acetate/hexane (1:9).
Step B. Preparation of 4-amino-2-chlorobenzotrifluoride
Tin(II) chloride dihydrate (4.97 mmol) was added to a solution of 2-chloro-4-nitro-1-trifluoromethylbenzene (4.14 mmol) in methanol in a single addition at room temperature and the mixture was stirred for 16 hours. The mixture was concentrated in vacuum and purified by chromatography, eluting with ethyl acetate/hexane (1:4 to 2:3) to give the title compound.
