3-(Trifluoromethyl)phenol → 2-(3-(Trifluoromethyl)phenoxy)-3-pyridinecarboxylic acid

HRID 1877344Notes

Reaction equation

HRID 1877344 reaction equation
Cl[C:2]1[N:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[F:11][C:12]([F:21])([F:20])[C:13]1[CH:14]=[C:15]([OH:19])[CH:16]=[CH:17][CH:18]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O.[Cu]I.[Cu]>[F:11][C:12]([F:20])([F:21])[C:13]1[CH:14]=[C:15]([CH:16]=[CH:17][CH:18]=1)[O:19][C:2]1[N:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5]

Participants

8

Reactant 3

HCID 73763-(Trifluoromethyl)phenolHCID 11430Potassium CarbonateHCID 762582-Chloronicotinic acid

Product 1

HCID 2158912-(3-(Trifluoromethyl)phenoxy)-3-pyridinecarboxylic acidYield 29.5%

Reagents, catalysts & solvents 4

HCID 23978CopperCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
140 °C

Procedure

To a solution of 2-chloro-nicotinic acid (1.0 g, 6.35 mmol, 1.0 equiv; [CAS RN 2942-59-8]) and 3-trifluoromethyl-phenol (1.03 g, 6.35 mmol, 1.0 equiv; [CAS RN 98-17-9]) in anhydrous DMF (5 mL) was added potassium carbonate (1.75 g, 12.69 mmol, 2.0 equiv; [CAS RN 584-08-7]), copper(I) iodide (0.12 g, 0.64 mmol, 0.1 equiv; [CAS RN 7681-65-4]) and copper(0) nanopowder with an averaged particle size of 100 nm (0.12 g, 1.90 mmol, 0.3 equiv; [CAS RN 7440-50-8]). The reaction mixture was heated by microwave irradiation to 140° C. for 30 min. The solvent was evaporated under reduced pressure and the crude reaction product taken up in water (25 mL) and filtered. The solution was adjusted to pH 4 by addition of acetic acid and the formed white precipitate filtered, washed with little cold water and dried under high vacuum providing 0.53 g (28%) of the title compound. 1H NMR (300 MHz, DMSO): δ7.26-7.30 (m, 1H), 7.43-7.50 (m, 2H), 7.57-7.66 (m, 2H), 8.26-8.29 (m, 2H). 19F NMR (282 MHz, DMSO): δ−61.0. MS (ISN): 282.1 [M−H]−.

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. customthe crude reaction product
  3. filtrationfiltered
  4. additionThe solution was adjusted to pH 4 by addition of acetic acid
  5. filtrationthe formed white precipitate filtered
  6. washwashed with little cold water
  7. customdried under high vacuum

Sources & evidence

ORD record
ord-1fd6a0513a824fcfac466f7bc54caa7c
Source dataset
uspto-grants-2012_11
Patent number
US08309734B2

Reaction notes

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