Potassium Carbonate → 2-(4-Methylsulfanyl-phenoxy)-nicotinic acid methyl ester

HRID 724278Notes

Reaction equation

HRID 724278 reaction equation
[CH3:1][O:2][C:3](=[O:11])[C:4]1[CH:9]=[CH:8][CH:7]=[N:6][C:5]=1Cl.[CH3:12][S:13][C:14]1[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[NH3:6].[CH3:1][O:2][C:3](=[O:11])[C:4]1[CH:9]=[CH:8][CH:7]=[N:6][C:5]=1[O:20][C:17]1[CH:18]=[CH:19][C:14]([S:13][CH3:12])=[CH:15][CH:16]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 140864-(Methylthio)phenolHCID 819931Methyl 2-chloronicotinate

Product 2

HCID 222AmmoniaHCID 587461792-(4-Methylsulfanyl-phenoxy)-nicotinic acid methyl esterYield 83.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

2-Chloronicotinic acid methyl ester (12 g, 69.9 mmol), 4-methylsulfanylphenol (9.80 g, 69.9 mmol) and potassium carbonate (14.5 g, 0.105 mol) were suspended in dimethylformamide (300 ml) and the reaction was heated to 65° C. and stirred at this temperature under nitrogen for 10 h. It was then heated to 90° C. and stirred at this temperature for 7 h, and then progressed to 100° C. and stirred for 16 h. The reaction was cooled to room temperature, concentrated under reduced pressure and the residue was diluted with water (300 ml). It was then extracted with diether (3×250 ml) and the combined organic extracts were washed with water (2×100 ml), dried over MgSO4 and the solvent removed under reduced pressure. The residue was purified by flash column chromatography on silica gel eluting with dichloromethane:methanol:concentrated aqueous ammonia (99.5:0.5:0.05, by volume) to give 2-(4-methylsulfanyl-phenoxy)-nicotinic acid methyl ester (8.0 g) as a white solid.

Workup

  1. temperatureIt was then heated to 90° C.
  2. stirringstirred at this temperature for 7 h
  3. customprogressed to 100° C.
  4. stirringstirred for 16 h
  5. temperatureThe reaction was cooled to room temperature
  6. concentrationconcentrated under reduced pressure
  7. additionthe residue was diluted with water (300 ml)
  8. extractionIt was then extracted with diether (3×250 ml)
  9. washthe combined organic extracts were washed with water (2×100 ml)
  10. dry with materialdried over MgSO4
  11. customthe solvent removed under reduced pressure
  12. customThe residue was purified by flash column chromatography on silica gel eluting with dichloromethane

Sources & evidence

ORD record
ord-48596fff8c7249958322525a6fe61c01
Source dataset
uspto-grants-2006_11
Patent number
US07141586B2

Reaction notes

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