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

HRID 709602Notes

Reaction equation

HRID 709602 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([C:13]([O:15][CH3:16])=[O:14])=[N:6][C:7]=1[O:8][CH2:9][CH:10]([CH3:12])[CH3:11].[F:17][C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][C:19]=1B(O)O.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:17][C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][C:19]=1[C:2]1[CH:3]=[CH:4][C:5]([C:13]([O:15][CH3:16])=[O:14])=[N:6][C:7]=1[O:8][CH2:9][CH:10]([CH3:12])[CH3:11]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 41572112-Fluoro-5-methoxyphenylboronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 117759996Methyl 5-bromo-6-isobutoxypicolinate

Product 1

HCID 117759827Methyl 5-(2-fluoro-5-methoxyphenyl)-6-isobutoxypicolinateYield 73.6%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

Under an argon atmosphere, to a solution of methyl 5-bromo-6-isobutoxypicolinate (698 mg), 2-fluoro-5-methoxyphenylboronic acid (454 mg), tris(dibenzylideneacetone)dipalladium(0) (65 mg) and 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (117 mg) in toluene (10 mL) was added 2.0 M aqueous sodium carbonate solution (2.67 mL), and the mixture was stirred at 100° C. for 30 min. The reaction mixture was filtered through celite, and water was added at room temperature. The reaction mixture was extracted with ethyl acetate, and the extract was washed with water and saturated brine. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (594 mg) as a pale-yellow oil.

Workup

  1. filtrationThe reaction mixture was filtered through celite, and water
  2. additionwas added at room temperature
  3. extractionThe reaction mixture was extracted with ethyl acetate
  4. washthe extract was washed with water and saturated brine
  5. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  6. customthe solvent was evaporated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-d9973712615948db9c2bcfd908899cf3
Source dataset
uspto-grants-2015_11
Patent number
US09181186B2

Reaction notes

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