2-Chloro-5-(trifluoromethyl)pyridine → 2-(5-Trifluoromethyl-pyridin-2-yl)-benzoic acid isopropyl ester

HRID 841774Notes

Reaction equation

HRID 841774 reaction equation
[CH:1]([O:4][C:5]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1B(O)O)=[O:6])([CH3:3])[CH3:2].Cl[C:17]1[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][N:18]=1>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>[CH:1]([O:4][C:5](=[O:6])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[C:17]1[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][N:18]=1)([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 923422-Chloro-5-(trifluoromethyl)pyridineHCID 53435142(2-(Isopropoxycarbonyl)phenyl)boronic acid

Product 1

HCID 698912952-(5-Trifluoromethyl-pyridin-2-yl)-benzoic acid isopropyl esterYield 70%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Procedure

2-(Isopropylcarboxy)-phenylboronic acid (S. Caron and J. M. Hawkins, J. Org. Chem. 1998, 63, 2054-2055) (2.2 g, 10.6 mmol) and 2-chloro-5-trifluoromethylpyridine (500 mg, 2.75 mmol) were dissolved in toluene. Tetrakis(triphenylphosphine)palladium (160 mg, 0.14 mmol) was added and the reaction vessel purged by alternating vacuum and nitrogen gas three times. 8 ml of a 10% sodium carbonate solution was added and the reaction mixture was heated at reflux for 1.5 h. The resulting mixture was extracted with ethyl acetate, the combined organic layers dried (magnesium sulfate), filtered and concentrated under vacuum. Purification of the residue by column chromatography eluting with 10% ethyl acetate in hexanes provided the title compound in approximately 70% yield.

Workup

  1. customthe reaction vessel purged
  2. addition8 ml of a 10% sodium carbonate solution was added
  3. temperaturethe reaction mixture was heated
  4. temperatureat reflux for 1.5 h
  5. extractionThe resulting mixture was extracted with ethyl acetate
  6. dry with materialthe combined organic layers dried (magnesium sulfate)
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum
  9. customPurification of the residue by column chromatography
  10. washeluting with 10% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-8bb323db14634dfba0d4059e3722cebe
Source dataset
uspto-grants-2002_04
Patent number
US06369075B1

Reaction notes

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