Ethanol → 6-(4-Fluorophenyl)picolinic acid

HRID 2237247

Reaction equation

HRID 2237247 reaction equation
Br[C:2]1([C:8]([OH:10])=[O:9])[CH:7]=[CH:6][CH:5]=[CH:4][NH:3]1.C([O-])([O-])=O.[Na+].[Na+].[F:17][C:18]1[CH:23]=[CH:22][C:21](B2OCC(C)(C)CO2)=[CH:20][CH:19]=1.CCO>COCCOC.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>[F:17][C:18]1[CH:23]=[CH:22][C:21]([C:4]2[N:3]=[C:2]([C:8]([OH:10])=[O:9])[CH:7]=[CH:6][CH:5]=2)=[CH:20][CH:19]=1

Participants

7

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 110200772-(4-Fluorophenyl)-5,5-dimethyl-1,3,2-dioxaborinaneHCID 210815642-Bromo-picolinic acid

Product 1

HCID 210817086-(4-Fluorophenyl)picolinic acidYield 46%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 2-bromo-picolinic acid (Aldrich, 2.02 g, 10 mmol) in DME containing 4 mL of 10% aq Na2CO3 was purged with Ar gas. To this mixture was added Pd(PPh3)4 followed by 2-(4-fluorophenyl)-5,5-dimethyl-1,3,2-dioxaborinane (Aldrich, 2.40 g, 11.5 mmol) and EtOH (20 mL), and the mixture was purged with Ar gas. The reaction mixture was heated at 100° C. for 2.5 h in a sealed tube. Additional 2-bromo-picolinic acid (900 mg) and Pd(PPh3)4 was added, and after purging with Ar gas it was heated at 100° C. for 4.5 h. Trifluoroacetic acid (20 mL) was added to the reaction and the mixture was concentrated in vacuo. MeOH (150 mL) was added to the residue and the insoluble material was filtered, and the filtrate solution was concentrated in vacuo. Purification of the resulting residue by flash column chromatography on silica gel eluting with EtOAc/MeOH/900:100 followed by EtOAc/MeOH/HOAc/700:1500:50 provided the desired product (1.0 g, 40% based on borinane starting material) as a white solid. 1H NMR (CD3OD) δ 8.01 (d, 1H, J=7.7 Hz), 7.94-7.87 (m, 3H), 7.73 (d, 1H, J=7.7 Hz), 7.13 (t, 2H, J=8.8 Hz); MS(ESI+) m/z 234 (M+H)+.

Workup

  1. customthe mixture was purged with Ar gas
  2. additionAdditional 2-bromo-picolinic acid (900 mg) and Pd(PPh3)4 was added
  3. customafter purging with Ar gas it
  4. temperaturewas heated at 100° C. for 4.5 h
  5. additionTrifluoroacetic acid (20 mL) was added to the reaction
  6. concentrationthe mixture was concentrated in vacuo
  7. additionMeOH (150 mL) was added to the residue
  8. filtrationthe insoluble material was filtered
  9. concentrationthe filtrate solution was concentrated in vacuo
  10. customPurification of the resulting residue by flash column chromatography on silica gel eluting with EtOAc/MeOH/900:100

Sources & evidence

ORD record
ord-45dc48a098f34cae9e332ea19b1a5ed9
Source dataset
uspto-grants-2010_05
Patent number
US07714138B2

Linked notes

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