2,5-Dichlorophenol → 4-(2,5-Dichloro-phenoxy)-6-methyl-nicotinic acid methyl ester

HRID 1025888Notes

Reaction equation

HRID 1025888 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.[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:15]=1[OH:21].C(=O)([O-])[O-].[K+].[K+].Cl>CN(C)C=O.[Cu]I.[Cu].C(OCC)(=O)C>[CH3:1][O:2][C:3](=[O:12])[C:4]1[C:9]([O:21][C:15]2[CH:16]=[C:17]([Cl:20])[CH:18]=[CH:19][C:14]=2[Cl:13])=[CH:8][C:7]([CH3:11])=[N:6][CH:5]=1

Participants

9

Reactant 4

HCID 662,5-DichlorophenolHCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 20691977Methyl 4-chloro-6-methylpyridine-3-carboxylate

Product 1

HCID 673204514-(2,5-Dichloro-phenoxy)-6-methyl-nicotinic acid methyl esterYield 48.5%

Reagents, catalysts & solvents 4

HCID 23978CopperCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 0.53 g (2.855 mmol) 4-chloro-6-methyl-nicotinic acid methyl ester (commercially available, CAS RN 886372-05-0) in 7.5 mL dry N,N-dimethylformamide was added 489 mg (2.998 mmol) 2,5-dichlorophenol, 789 mg (5.711 mmol) potassium carbonate, 54 mg (0.286 mmol) copper(I)iodide and 54 mg (0.857 mmol) copper nanopowder (avg. particel size 100 nm). The reaction mixture was stirred at 120° C. for 3 hours and then poured on 30 mL 1M aqueous hydrochloric acid and 30 mL ethyl acetate. The layers were separated and the aqueous layer was extracted with 30 mL ethyl acetate. The combined organic layers were washed with 30 mL brine, dried over magnesium sulfate, filtered and concentrated under vacuum. The residue was purified by silica gel chromatography using a MPLC system (20 g silica gel column, CombiFlash Companion, Isco Inc.) with a gradient of n-heptane:ethyl acetate (100:0 to 0:100), to give 432 mg (48%) of the compound as a light yellow solid. MS (ESI): m/z=312.019 [M+H]+.

Workup

  1. customThe layers were separated
  2. extractionthe aqueous layer was extracted with 30 mL ethyl acetate
  3. washThe combined organic layers were washed with 30 mL brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-81f9c5abcab24249948d8a0bb40ae630
Source dataset
uspto-grants-2014_05
Patent number
US08729091B2

Reaction notes

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