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

HRID 709762Notes

Reaction equation

HRID 709762 reaction equation
Cl[C:2]1[C:11]([O:12][CH2:13][CH:14]([CH3:16])[CH3:15])=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][N:3]=1.[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[C:11]([O:12][CH2:13][CH:14]([CH3:16])[CH3:15])=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 41572112-Fluoro-5-methoxyphenylboronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 117760029Methyl 6-chloro-5-isobutoxynicotinate

Product 1

HCID 117760303Methyl 6-(2-fluoro-5-methoxyphenyl)-5-isobutoxynicotinateYield 72.3%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

Under an argon atmosphere, to a solution of methyl 6-chloro-5-isobutoxynicotinate (1.84 g) in toluene (25 mL) were added 2-fluoro-5-methoxyphenylboronic acid (2.21 g), tris(dibenzylideneacetone)dipalladium(0) (318 mg), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (570 mg) and 2.0 M aqueous sodium carbonate solution (13.0 mL), and the mixture was stirred at 100° C. for 1 hr. 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 (1.82 g) as a 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-ac99610d5b6540c79654d0e51536658f
Source dataset
uspto-grants-2015_11
Patent number
US09181186B2

Reaction notes

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