Sodium Carbonate → 3-Methyl-5-(3-trifluoromethyl-phenyl)-pyridine-2-carboxylic acid methyl ester

HRID 1517053Notes

Reaction equation

HRID 1517053 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:10]([CH3:11])=[CH:9][C:8](Br)=[CH:7][N:6]=1)=[O:4].[F:13][C:14]([F:25])([F:24])[C:15]1[CH:16]=[C:17](B(O)O)[CH:18]=[CH:19][CH:20]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.[Pd](Cl)Cl>[CH3:1][O:2][C:3]([C:5]1[C:10]([CH3:11])=[CH:9][C:8]([C:19]2[CH:18]=[CH:17][CH:16]=[C:15]([C:14]([F:25])([F:24])[F:13])[CH:20]=2)=[CH:7][N:6]=1)=[O:4]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27343883-(Trifluoromethyl)phenylboronic acidHCID 45789787Methyl 5-bromo-3-methylpicolinate

Product 1

HCID 574411233-Methyl-5-(3-trifluoromethyl-phenyl)-pyridine-2-carboxylic acid methyl esterYield 87.2%

Reagents, catalysts & solvents 2

HCID 24290Palladium ChlorideCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

To a degassed solution of 8.35 g (36.3 mmol) of 5-bromo-3-methyl-pyridine-2-carboxylic acid methyl ester [Wu, G. G.; Wong, Y.-S.; Poirier, M. Organic Letters (1999), 1(5), 745-747] in 180 ml of dioxane were added 13.79 g (72.6 mmol) of 3-(trifluoromethyl)phenyl boronic acid and 11.54 g (108.9 mmol) of sodium carbonate (dissolved in 55 ml of H2O). While stirring, 1.33 g (1.89 mmol) of (1,1′-bis-diphenylphosphino)-ferrocene)palladium-(II)dichloride (1:1 complex with CH2Cl2) was added and the reaction mixture was stirred at RT for 4 hours, then heated up to 50° C. After 90 min, it was cooled down to RT, poured into crashed ice and extracted twice with EtOAc; the organic phases were washed with water, dried over magnesium sulfate, filtered and evaporated. The residue was purified by flash column chromatography (heptane/EtOAc 9:1 to 1:1) to give 9.35 g (87%) of the title compound as light yellow solid. MS: 296.1 (MH+).

Workup

  1. stirringthe reaction mixture was stirred at RT for 4 hours
  2. temperatureit was cooled down to RT
  3. additionpoured
  4. extractionextracted twice with EtOAc
  5. washthe organic phases were washed with water
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by flash column chromatography (heptane/EtOAc 9:1 to 1:1)

Sources & evidence

ORD record
ord-7b62cc744e34496cbd16ec78ba909ced
Source dataset
uspto-grants-2012_07
Patent number
US08227613B2

Reaction notes

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