4-Fluoro-3-(trifluoromethyl)aniline → HCID 57501605, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of commercially available 2,4,6-trichloropyrimidine (XXI) (10.0 g, 52.5 mmol) and diisopropylethylamine (7.7 g, 52.5 mmol) in dioxane (50 mL) under inert atmosphere was added a solution of 4-fluoro-3-trifluoromethylaniline (XX) (9.70 g, 52.5 mmol) in dioxane (150 mL) and then the mixture was heated to 80° C. and stirred for 12 h. The mixture was cooled to ambient temperature and diluted with ether (200 mL) and water (50 mL). The organic phase was separated, successively rinsed with 1N aqueous hydrochloric acid and saturated brine, dried over anhydrous sodium sulfate and filtered. Removal of the volatiles under vacuum on a rotary evaporator gave a gummy solid. This solid was purified by flash column chromatography (silica gel, hexanes/ethyl acetate) to give two isomeric products (2,6-dichloropyrimidin-4-yl)-(4-fluoro-3-trifluoromethylphenyl)amine (XXII) (11.2 g, 63% yield) and (4,6-dichloropyrimidin-2-yl)-(4-fluoro-3-trifluoromethylphenyl)amine (XXIII) (5.2 g 29% yield). Compound XXII: m.p. 129-130° C.; 1H NMR (CDCl3) δ 7.60 (m, 2H), 7.28 (m, 1H), 6.45 (s, 1H); GCMS (m/z) 325 (M−1+); Compound XXIII: m.p.=102-104° C.; 1H NMR (CDCl3) δ 7.86 (dd, J=6.6, 2.7 Hz, 1H), 7.76 (m, 1H), 7.20 (t, J=6.6 Hz,1H), 6.84 (s, 1H); GCMS (m/z) 325 (M−1+)

Provenance & Evidence