Glycol monoethyl ether → 4-Fluoro-2-(2-fluoro-phenylamino)-benzoic acid

HRID 1887808Notes

Reaction equation

HRID 1887808 reaction equation
Br[C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[F:12][C:13]1[CH:19]=[CH:18][CH:17]=[CH:16][C:14]=1[NH2:15].C(=O)([O-])[O-].[K+].[K+].C(OCCO)C>[Cu].[Cu]I.O>[F:11][C:9]1[CH:8]=[CH:7][C:3]([C:4]([OH:6])=[O:5])=[C:2]([NH:15][C:14]2[CH:16]=[CH:17][CH:18]=[CH:19][C:13]=2[F:12])[CH:10]=1

Participants

8

Reactant 4

HCID 8076Glycol monoethyl etherHCID 95842-FluoroanilineHCID 11430Potassium CarbonateHCID 12681692-Bromo-4-fluorobenzoic acid

Product 1

HCID 712089244-Fluoro-2-(2-fluoro-phenylamino)-benzoic acidYield 113.4%

Reagents, catalysts & solvents 3

HCID 23978CopperCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolvent

Conditions

Temperature
135 °C

Procedure

In a 50 mL round bottom flask, 2-bromo-4-fluorobenzoic acid (12.78 g, 58.4 mmol), 2-fluoroaniline (7.33 mL, 75.9 mmol), potassium carbonate (9.68 g, 70.0 mmol), copper (0.371 g, 5.84 mmol) and copper (I) iodide (0.556 g, 2.92 mmol) were added to 2-ethoxyethanol (50 mL). The mixture was heated to 135° C. overnight. The mixture was cooled and 100 mL of water was added. The slurry was stirred at room temperature overnight. The slurry was filtered through a bed of celite and washed with 2-ethoxyethanol. The pH of the filtrate was adjusted to 2 using 4N HCl and the solid was filtered off. The solid was then dried in high vacuum to give 4-fluoro-2-(2-fluoro-phenylamino)-benzoic acid (16.5 g, >100% yield).

Workup

  1. temperatureThe mixture was cooled
  2. filtrationThe slurry was filtered through a bed of celite
  3. washwashed with 2-ethoxyethanol
  4. filtrationthe solid was filtered off
  5. customThe solid was then dried in high vacuum

Sources & evidence

ORD record
ord-5db5f5e709b74ecf85be853dbf253b10
Source dataset
uspto-grants-2013_08
Patent number
US08501732B2

Reaction notes

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