Trifluoroacetic acid → 2,3-Dichloro-4-fluoroaniline

HRID 1512347Notes

Reaction equation

HRID 1512347 reaction equation
C(OC(=O)[NH:7][C:8]1[CH:13]=[CH:12][C:11]([F:14])=[C:10]([Cl:15])[C:9]=1[Cl:16])(C)(C)C.FC(F)(F)C(O)=O.C(=O)(O)[O-].[Na+]>ClCCl>[Cl:16][C:9]1[C:10]([Cl:15])=[C:11]([F:14])[CH:12]=[CH:13][C:8]=1[NH2:7]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 68582591HCID 68582591, compound

Product 1

HCID 231628652,3-Dichloro-4-fluoroanilineYield 81%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To an oven-dried, N2-purged, 100-mL, round-bottomed flask containing a magnetic stir bar were added the product of Example 192B (3.08 g, 11.0 mmol) and dichloromethane (25 mL). The flask was sealed with a septum and cooled to 0° C. in an ice bath. Trifluoroacetic acid (18 mL) was added dropwise via syringe. The brown solution was stirred at 0° C. for 30 minutes and then allowed to warm to room temperature for 2 hours. The mixture was transferred to a large Erlenmeyer flask and the acid was neutralized by the careful addition of saturated aqueous sodium bicarbonate. The mixture was transferred to a separatory funnel and extracted with dichloromethane (3×25 mL). The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated by rotary evaporator to give a brown semi-solid. The product was purified by flash chromatography (silica gel: 20% ethyl acetate, 80% hexanes, product Rf˜0.3) to give 1.49 g (81%) of the title compound as a pink solid. MS (ESI−) m/z 178.0 (M−H); 1H NMR (DMSO-d6) δ 5.53 (br s, 2H), 6.77 (dd, J=9.2, 5.1 Hz, 1H), 7.13 (dd, J=9.2, 9.2 Hz, 1H).

Workup

  1. customTo an oven-dried, N2-purged
  2. addition100-mL, round-bottomed flask containing a magnetic stir bar
  3. customThe flask was sealed with a septum
  4. temperatureto warm to room temperature for 2 hours
  5. customThe mixture was transferred to a separatory funnel
  6. extractionextracted with dichloromethane (3×25 mL)
  7. dry with materialThe combined organic extracts were dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated by rotary evaporator
  10. customto give a brown semi-solid
  11. customThe product was purified by flash chromatography (silica gel: 20% ethyl acetate, 80% hexanes, product Rf˜0.3)

Sources & evidence

ORD record
ord-0498e4c196db46f7a3d4588cc699189e
Source dataset
uspto-grants-2012_07
Patent number
US08217067B2

Reaction notes

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