Nitric Acid → 4-Chloro-3-nitro-6-(2-trifluoromethyl-phenyl)-pyridin-2-ylamine
Reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[C:14]([F:17])([F:16])[F:15])[N:5]=[C:4]([NH2:18])[CH:3]=1.OS(O)(=O)=O.[N+:24]([O-])([OH:26])=[O:25]>>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[C:14]([F:15])([F:16])[F:17])[N:5]=[C:4]([NH2:18])[C:3]=1[N+:24]([O-:26])=[O:25]Participants
4
Conditions
- Temperature
- 0 °C
Procedure
4-Chloro-6-(2-trifluoromethyl-phenyl)-pyridin-2-ylamine (617.5 mg, 2.27 mmol, prepared as described in STEP A above) was cooled to 0° C. and treated slowly with H2SO4 (10 mL). The mixture was stirred at 0° C. for 1 h. Nitric acid (133 μL, 2.94 mmol) was added slowly, and the mixture continued to stir at 0° C. for an additional 1.5 h. Ice (50 mL) was added. A precipitate formed and was filtered, dissolved in DCM (70 mL), and washed with saturated aqueous NaHCO3 (70 mL). The aqueous layer was extracted with DCM (30 mL). The combined organic extracts were dried over MgSO4 and concentrated in vacuo. The residue was purified on a 40-g SEPRA Si 35 SPE column (Flow rate=20 mL/min; Eluent=EtOAc-hexanes, 1:19 for 15 min, then 1:19 to 1:3 over 40 min) to yield 4-chloro-3-nitro-6-(2-trifluoromethyl-phenyl)-pyridin-2-ylamine as a yellow solid. The basic mother liquor and acidic filtrate were carefully combined, made basic with 1 N aqueous NaOH, and extracted twice with DCM (100 mL). The combined organic extracts were dried over MgSO4 and concentrated in vacuo to yield additional product. 1H-NMR (400 MHz, CDCl3) δ: 7.76-7.90 (m, 1H), 7.55-7.71 (m, 2H), 7.46 (d, J=7.3 Hz, 1H), 6.93 (s, 1H), 6.11 (br. s., 2H). Mass Spectrum (LCMS, APCI pos.): Calculated for C12H7N3O2ClF3: 318.0 (M+H). Measured: 318.0.