Sodium Carbonate → Methyl 6-chloro-5-(2-fluoro-5-methoxyphenyl)picolinate

HRID 1049522Notes

Reaction equation

HRID 1049522 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([C:9]([O:11][CH3:12])=[O:10])=[N:6][C:7]=1[Cl:8].[F:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][C:15]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.O>[Cl:8][C:7]1[N:6]=[C:5]([C:9]([O:11][CH3:12])=[O:10])[CH:4]=[CH:3][C:2]=1[C:15]1[CH:16]=[C:17]([O:20][CH3:21])[CH:18]=[CH:19][C:14]=1[F:13]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 41572112-Fluoro-5-methoxyphenylboronic acidHCID 46311197Methyl 5-bromo-6-chloropicolinate

Product 1

HCID 117759829Methyl 6-chloro-5-(2-fluoro-5-methoxyphenyl)picolinateYield 92.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

Under an argon atmosphere, to a solution of methyl 5-bromo-6-chloropicolinate (12.0 g) in toluene (300 mL) were added 2-fluoro-5-methoxyphenylboronic acid (9.83 g), [1,1-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane adduct (1.00 g) and a solution of sodium carbonate (14.8 g) in water (60 mL), and the mixture was stirred at 80° C. for 2 hr. The reaction mixture was concentrated under reduced pressure, and diluted with water. The reaction mixture was extracted with ethyl acetate, and the extract was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was recrystallized from ethyl acetate to give the title compound (13.1 g) as pale-yellow crystals.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additiondiluted with water
  3. extractionThe reaction mixture was extracted with ethyl acetate
  4. washthe extract was washed with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customThe solvent was evaporated under reduced pressure
  7. customthe residue was recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-32e9547c9b55425fa8516df7766ef020
Source dataset
uspto-grants-2016_07
Patent number
US09382188B2

Reaction notes

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