Ethyl Acetate → 4-(4-Bromo-2,5-dichloro-phenoxy)-6-methyl-nicotinic acid methyl ester

HRID 1967045

Reaction equation

HRID 1967045 reaction equation
[CH3:1][O:2][C:3](=[O:12])[C:4]1[C:9](Cl)=[CH:8][C:7]([CH3:11])=[N:6][CH:5]=1.[Br:13][C:14]1[C:19]([Cl:20])=[CH:18][C:17]([OH:21])=[C:16]([Cl:22])[CH:15]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C(OCC)(=O)C>CC1C=CC=CC=1C.O>[CH3:1][O:2][C:3](=[O:12])[C:4]1[C:9]([O:21][C:17]2[CH:18]=[C:19]([Cl:20])[C:14]([Br:13])=[CH:15][C:16]=2[Cl:22])=[CH:8][C:7]([CH3:11])=[N:6][CH:5]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 160224-Bromo-2,5-dichlorophenolHCID 20691977Methyl 4-chloro-6-methylpyridine-3-carboxylate

Product 1

HCID 673205494-(4-Bromo-2,5-dichloro-phenoxy)-6-methyl-nicotinic acid methyl esterYield 8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 7237O-XyleneSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 1.25 g (6.734 mmol) 4-chloro-6-methyl-nicotinic acid methyl ester (commercially available, CAS RN 886372-05-0) in 30 mL o-xylene was added 1.792 g (7.408 mmol) 4-bromo-2,5-dichlorophenol (commercially available, CAS RN 1940-42-7), 0.502 g (1.347 mmol) tetrakis(acetonitrile)copper (I) hexafluorophosphate (commercially available, CAS RN 64443-05-6) and 5.536 g (16.836 mmol) cesium carbonate. The reaction mixture was stirred at 120° C. for 20 hours and was then allowed to cool to room temperature. Ethyl acetate (50 mL) and water (50 mL) was added and stirring was continued for another 10 minutes. The reaction mixture was filtered over Dicalite® speed plus (Acros) and the layers were separated. The aqueous layer was extracted with 200 mL ethyl acetate and the combined organic layers were washed with 200 mL brine, dried over magnesium sulfate, filtered and concentrated under vacuum. The residue was purified by silica gel chromatography using a MPLC system (50 g silica gel column, CombiFlash Companion, Isco Inc.) and a gradient of n-heptane:ethyl acetate (100:0 to 40:60) to give 200 mg (8%) of the title compound as a light yellow solid. MS (Turbo Spray): m/z=391.9 [M+H]+.

Workup

  1. temperatureto cool to room temperature
  2. stirringstirring
  3. waitwas continued for another 10 minutes
  4. filtrationThe reaction mixture was filtered over Dicalite® speed plus (Acros)
  5. customthe layers were separated
  6. extractionThe aqueous layer was extracted with 200 mL ethyl acetate
  7. washthe combined organic layers were washed with 200 mL brine
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under vacuum
  11. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-778d6aed3850437f87725ec92ab0754e
Source dataset
uspto-grants-2013_04
Patent number
US08420647B2

Linked notes

Loading…