Sodium Carbonate → 2-(4-Trifluoromethyl-phenyl)-nicotinic acid ethyl ester

HRID 841778Notes

Reaction equation

HRID 841778 reaction equation
Cl[C:2]1[N:12]=[CH:11][CH:10]=[CH:9][C:3]=1[C:4]([O:6][CH2:7][CH3:8])=[O:5].[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(COC)OC.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>[CH2:7]([O:6][C:4](=[O:5])[C:3]1[CH:9]=[CH:10][CH:11]=[N:12][C:2]=1[C:18]1[CH:19]=[CH:20][C:15]([C:14]([F:25])([F:24])[F:13])=[CH:16][CH:17]=1)[CH3:8]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27343894-(Trifluoromethyl)phenylboronic acidHCID 2796614Ethyl chloronicotinate

Product 1

HCID 579874152-(4-Trifluoromethyl-phenyl)-nicotinic acid ethyl esterYield 109.7%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent2×

Procedure

Ethyl 2-chloro-nicotinate (1.86 g, 10.0 mmol)was dissolved in 10 ml of dimethoxyethane. Tetrakis(triphenylphosphine)palladium (347 mg, 0.3 mmol) was added and the reaction vessel purged by alternating vacuum and nitrogen gas three times. A solution of 4-trifluoromethylphenylboronic acid (2.09 g, 11.0 mmol) in 20 ml of dimethoxyethane was added to the reaction mixture followed by 10 ml of a 2M sodium carbonate solution. The reaction mixture was heated at 90 C. for 1.5 h before being cooled and extracted with 150 ml of ether. The organic layer was washed with 50 ml of 2N NaOH, 2×50 ml water, and brine before being dried (magnesium sulfate), filtered and concentrated under vacuum to afford 3.24 g of a brown oil. This material was purified by silica gel chromatography eluting with 5 to 10% ethyl acetate in hexanes to afford 2.34 g of the title compound as a pale yellow oil.

Workup

  1. customthe reaction vessel purged
  2. temperatureThe reaction mixture was heated at 90 C
  3. temperaturefor 1.5 h before being cooled
  4. extractionextracted with 150 ml of ether
  5. washThe organic layer was washed with 50 ml of 2N NaOH, 2×50 ml water, and brine
  6. dry with materialbefore being dried (magnesium sulfate)
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-4365f14320184343ba06d6f64413c221
Source dataset
uspto-grants-2002_04
Patent number
US06369075B1

Reaction notes

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