Nitric Acid → 4-Chloro-3-nitro-6-(2-trifluoromethyl-phenyl)-pyridin-2-ylamine

HRID 1191191Notes

Reaction equation

HRID 1191191 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

Reactant 3

HCID 944Nitric AcidHCID 1118Sulfuric AcidHCID 674122194-Chloro-6-(2-trifluoromethyl-phenyl)-pyridin-2-ylamine

Product 1

HCID 674111324-Chloro-3-nitro-6-(2-trifluoromethyl-phenyl)-pyridin-2-ylamine

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.

Workup

  1. stirringto stir at 0° C. for an additional 1.5 h
  2. customA precipitate formed
  3. filtrationwas filtered
  4. dissolutiondissolved in DCM (70 mL)
  5. washwashed with saturated aqueous NaHCO3 (70 mL)
  6. extractionThe aqueous layer was extracted with DCM (30 mL)
  7. dry with materialThe combined organic extracts were dried over MgSO4
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified on a 40-g SEPRA Si 35 SPE column (Flow rate=20 mL/min
  10. waitEluent=EtOAc-hexanes, 1:19 for 15 min

Sources & evidence

ORD record
ord-074d20d638f24cfbb878ebdab22d8faa
Source dataset
uspto-grants-2014_03
Patent number
US08680098B2

Reaction notes

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