Toluene → 5-Phenylnicotinic Acid

HRID 1171491Notes

Reaction equation

HRID 1171491 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8].[C:11]1(B(O)O)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C(=O)([O-])[O-].[Na+].[Na+].C1(C)C=CC=CC=1>C(O)C.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.O>[C:11]1([C:2]2[CH:3]=[N:4][CH:5]=[C:6]([CH:10]=2)[C:7]([OH:9])=[O:8])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

8

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 887075-Bromonicotinic acid

Product 1

HCID 3461605-Phenylnicotinic AcidYield 67.2%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent2×HCID 962WaterSolvent2×

Procedure

5-Bromonicotinic acid (500 mg, 2.48 mmol, 1 eq.), phenylboronic acid (454 mg, 3.71 mmol, 1.5 eq.), tetrakis(triphenylphosphine)palladium(0) (143 mg, 0.124 mmol, 0.05 eq.), and sodium carbonate (787 mg, 7.43 mmol, 3 eq.) were mixed in ethanol (5 mL), toluene (25 mL), and water (5 mL) at room temperature under nitrogen. The reaction was then refluxed for 20 hours. Worked up by adding water then stripping off the ethanol. Rinsed the aqueous layer 2 times with diethyl ether. Adjusted the aqueous layer pH=3 with conc. HCl. The acidic aqueous layer was extracted 3 times with ethyl acetate and a little THF. The ethyl acetate/THF layers were combined, dried over sodium sulfate and stripped to give 5-phenylnicotinic acid (332 mg) as a white solid. Yield=67%. LCMS detects (M+H)+=198.1.

Workup

  1. customat room temperature
  2. temperatureThe reaction was then refluxed for 20 hours
  3. washRinsed the aqueous layer 2 times with diethyl ether
  4. extractionThe acidic aqueous layer was extracted 3 times with ethyl acetate
  5. dry with materialdried over sodium sulfate

Sources & evidence

ORD record
ord-28f8113b50fc4d9cb5b01135cbee8e9e
Source dataset
uspto-grants-2010_11
Patent number
US07829571B2

Reaction notes

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