Hydrochloric Acid → 3-Pyridinecarboxylic acid, 2-(2,4-dichlorophenoxy)-

HRID 1877363Notes

Reaction equation

HRID 1877363 reaction equation
Cl[C:2]1[N:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[Cl:11][C:12]1[CH:17]=[C:16]([Cl:18])[CH:15]=[CH:14][C:13]=1[OH:19].C(=O)([O-])[O-].[Cs+].[Cs+].Cl>C1(C)C=CC=CC=1.O.CC#N.CC#N.CC#N.CC#N.F[P-](F)(F)(F)(F)F.[Cu+]>[Cl:11][C:12]1[CH:17]=[C:16]([Cl:18])[CH:15]=[CH:14][C:13]=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 4

HCID 313Hydrochloric AcidHCID 84492,4-DichlorophenolHCID 10796Cesium carbonateHCID 762582-Chloronicotinic acid

Product 1

HCID 2158923-Pyridinecarboxylic acid, 2-(2,4-dichlorophenoxy)-

Reagents, catalysts & solvents 3

HCID 11068737tetrakis(acetonitrile)copper(I) hexafluorophosphateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

To a solution of 2-chloro-nicotinic acid (2.15 g, 13.65 mmol, 1.0 equiv; [CAS RN 2942-59-8]) and 2,4-dichloro-phenol (2.22 g, 13.65 mmol, 1.0 equiv; [CAS RN 120-83-2]) in toluene (40 mL) was added caesium carbonate (8.89 g, 27.29 mmol, 2.0 equiv; [CAS RN 534-17-8]) and tetrakis(acetonitrile)copper(I) hexafluorophosphate (1.02 g, 2.73 mmol, 0.2 equiv; [CAS RN 64443-05-6]). The reaction mixture was heated to reflux over night. The solvent was evaporated under reduced pressure and the crude reaction product taken up in water (100 mL) acidified to pH 1 by addition of a solution of 1 M HCl and extracted with ethyl acetate (3×100 mL). The combined organic phases were dried over MgSO4 and the product purified by silica column chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of dichloromethane/methanol affording 1.69 g (44%) of the title compound as an off-white solid. 1H NMR (400 MHz, DMSO): δ7.26 (dd, J=7.6 Hz, J=4.8 Hz, 1H), 7.36 (d, J=8.7 Hz, 1H), 7.49 (dd, J=8.7 Hz, J=2.6 Hz, 1H), 7.76 (d, J=2.4 Hz, 1H), 8.25 (dd, J=4.8 Hz, J=2.2 Hz, 1H), 8.30 (dd, J=7.5 Hz, J=2.2 Hz, 1H), 13.33 (s, 1H). MS (ISN): 282.3 [M−H]−.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux over night
  3. customThe solvent was evaporated under reduced pressure
  4. customthe crude reaction product
  5. extractionextracted with ethyl acetate (3×100 mL)
  6. dry with materialThe combined organic phases were dried over MgSO4
  7. customthe product purified by silica column chromatography
  8. washeluting with a gradient of dichloromethane/methanol affording 1.69 g (44%) of the title compound as an off-white solid

Sources & evidence

ORD record
ord-d5b1c8c62093478d956402d0bc540093
Source dataset
uspto-grants-2012_11
Patent number
US08309734B2

Reaction notes

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