Potassium Carbonate → 6-(3-Fluorophenyl)nicotinic acid

HRID 602075Notes

Reaction equation

HRID 602075 reaction equation
[F:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[CH:6][CH:7]=1.C([O-])([O-])=O.[K+].[K+].Cl[C:18]1[CH:26]=[CH:25][C:21]([C:22]([OH:24])=[O:23])=[CH:20][N:19]=1>O.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>[F:1][C:2]1[CH:3]=[C:4]([C:18]2[CH:26]=[CH:25][C:21]([C:22]([OH:24])=[O:23])=[CH:20][N:19]=2)[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 792226-Chloronicotinic acidHCID 27339863-Fluorophenylboronic acid

Product 1

HCID 247299726-(3-Fluorophenyl)nicotinic acidYield 97.8%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

3-Fluorophenylboronic acid (39.5 g, 0.282 mol), a solution of K2CO3 (150 g) in water (700 mL), [Bu4N]Br (3.5 g, 0.0107 mol), and Pd(PPh3)4 (12.4 g, 0.0107 mol) were added to a solution of 6-chloronicotinic acid (37.0 g, 0.235 mol) in toluene. The reaction mixture was stirred under reflux for 20 h. After cooling, the reaction mixture was filtered and acidified with 2 M HCl to pH 3. The formed precipitate was separated by filtration and dried to give 6-(3-fluorophenyl)nicotinic acid (49.9 g). 1H NMR (400 MHz, DMSO-d6) δppm 7.29 (td, J=8.46, 2.42 Hz, 1H) 7.50-7.56 (m, 1H) 7.93 (dd, J=10.47, 2.15 Hz, 1 H) 7.97 (d, J=7.79 Hz, 1 H) 8.11 (d, J=8.06 Hz, 1H) 8.30 (dd, J=8.32, 2.15 Hz, 1H) 9.11 (d, J=1.88 Hz, 1 H), 13.48 (bs, 1H).

Workup

  1. temperatureunder reflux for 20 h
  2. temperatureAfter cooling
  3. filtrationthe reaction mixture was filtered
  4. customThe formed precipitate was separated by filtration
  5. customdried

Sources & evidence

ORD record
ord-1a8718c19ea043169ece39bf2b7283a8
Source dataset
uspto-grants-2011_03
Patent number
US07902373B2

Reaction notes

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