Ethyl Acetate → 6-Methyl-2-(4-trifluoromethylphenyl)nicotinic acid methyl ester

HRID 423240Notes

Reaction equation

HRID 423240 reaction equation
[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[N:6][C:5]=1Cl.[F:13][C:14]([F:25])([F:24])[C:15]1[CH:20]=[CH:19][C:18](B(O)O)=[CH:17][CH:16]=1.C(=O)([O-])[O-].[Na+].[Na+].C(OCC)(=O)C>C(O)C.C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[N:6][C:5]=1[C:18]1[CH:19]=[CH:20][C:15]([C:14]([F:25])([F:24])[F:13])=[CH:16][CH:17]=1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 27343894-(Trifluoromethyl)phenylboronic acidHCID 13055804Methyl 2-chloro-6-methylpyridine-3-carboxylate

Product 1

HCID 586297476-Methyl-2-(4-trifluoromethylphenyl)nicotinic acid methyl esterYield 87.2%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

2-Chloro-6-methylnicotinic acid methyl ester (18.6 g) and 4-trifluoromethylphenylboronic acid (22.0 g) were dissolved in a mixed solvent of ethanol (100 mL) and toluene (100 mL), and to this solution were added 2M sodium carbonate (100 mL) and tetrakis(triphenylphosphine)palladium(0) (2.90 g). The mixture was stirred at 120° C. for 3 hours under heating. Ethyl acetate (200 mL) was added to the reaction solution. The aqueous layer was separated off. The organic layer was washed successively with 0.1N sodium hydroxide, water, and saturated brine, dried over sodium sulfate, and concentrated. The residue was purified by column chromatography on silica gel with (hexane:ethyl acetate=1:4, v/v) to give the title compound (25.8 g) as a colorless oil.

Workup

  1. temperatureunder heating
  2. customThe aqueous layer was separated off
  3. washThe organic layer was washed successively with 0.1N sodium hydroxide, water, and saturated brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography on silica gel with (hexane:ethyl acetate=1:4, v/v)

Sources & evidence

ORD record
ord-1156175ecb6640ada6b87d32dc2228a9
Source dataset
uspto-grants-2012_01
Patent number
US08101774B2

Reaction notes

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