3-Nitro-5-(trifluoromethyl)benzoic acid

Reference Example 95 tert-butyl (3R*, 4R*)-4-{[[3-chloro-5-(trifluoromethyl)benzyl](methyl)amino]carbonyl}-3-(4-fluoro-2-methylphenyl)piperidine-1-carboxylate(Step 1)To a solution of 3-trifluoromethylbenzoic acid (203.4 g) in concentrated sulfuric acid (880 mL) was added 90percent fuming nitric acid (210 mL) at 0° C. over 1 hr. The mixture was stirred at 35° C. for 3 hr, and slowly poured onto ice (about 1 kg). The precipitate was filtrated with water (500 mL), and dissolved in ethyl acetate (500 mL). The ethyl acetate solution was washed with water and dried, and the solvent was evaporated under reduced pressure to give 3-nitro-5-(trifluoromethyl)benzoic acid (232.5 g, 92percent) as a white powder. Fuming nitric acid (5.5 mL) was added dropwise into a mixtureof 3-trifluoromethylbenzoic acid (5 g, 0.026 mol) and concentratedsulfuric acid (23 mL) under vigorous stirring. The reaction mixturewas stirred for 3 h at rt and then poured on ice. The crude productwas filtered, dissolved in EtOAc (30 mL) and washed with water(2 x 25 mL) and brine (1 x 25 mL). The organic layer was dried overanhydrous Na2SO4 and evaporated under reduced pressure. Yield:87percent as a light yellow solid; mp 128-130 °C. 1H NMR (500 MHz, acetone) δ 9.00 (t, J = 1.8 Hz, 1H), 8.78 (t, J = 1.9 Hz, 1H), 8.66 (t, J = 1.7 Hz, 1H). 13C NMR (126 MHz, acetone) δ 164.52, 149.77, 134.72, 132.76 (q, J = 34.2 Hz), 132.37 (q, J = 3.6 Hz), 128.46, 125.20 (q, J = 3.9 Hz), 123.72 (q, J =272.4 Hz).Step 1 : 3-Nitro-5-(trifluoromethyl)benzoic acid To a mixture of 3-(trifluoromethyl)benzoic acid (5 g, 26.3 mmol) in HTo a mixture of 3- (trifluoromethyl) benzoic acid (5 g 26.3 mmol) in sulfuric acid (50 ml 938 mmol) was added nitric acid (3.53 ml 79 mmol) . The mixture was stirred at 0 for 15min and warmed to 90 over 1 hour. Then the mixture was added to ice water dropwise. The mixture was then filtered to give a white solid of 3-nitro-5- (trifluoromethyl) benzoic acid (5 g 20.20 mmol 77yield)

Molecular Weight:235.12
XLogP3:2.2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:7
Rotatable Bond Count:1
Exact Mass:235.00924210
Monoisotopic Mass:235.00924210
Topological Polar Surface Area:83.1
Heavy Atom Count:16
Complexity:299
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes