Hydrochloric Acid → 6-(4-Fluorophenyl)nicotinic acid

HRID 915645Notes

Reaction equation

HRID 915645 reaction equation
C[O:2][C:3]([C:5]1[CH:6]=[N:7][C:8]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)=[CH:9][CH:10]=1)=[O:4].[OH-].[Na+].Cl>O1CCCC1>[F:17][C:14]1[CH:15]=[CH:16][C:11]([C:8]2[N:7]=[CH:6][C:5]([C:3]([OH:4])=[O:2])=[CH:10][CH:9]=2)=[CH:12][CH:13]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 110317126-(4-Fluorophenyl)pyridine-3-carboxylic acid methyl ester

Product 1

HCID 227301866-(4-Fluorophenyl)nicotinic acidYield 37%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Combine 6-bromopyridine-3-carboxylic acid methyl ester (1.03 g, 4.78 mmol), 4-fluorophenylboronic acid (1.88 g, 13.41 mmol), and cesium fluoride (2.55 g, 16.78 mmol) in dimethylformamide (25 mL) and water (4 mL) with stirring. Place the hetereogeneous reaction mixture, open to the air, in an oil bath maintained at 80° C. After 5 minutes of heating, add Pd(OAc)2 (150 mg, 0.67 mmol) in one portion. After 17 hours, cool the reaction to room temperature, dilute with ethyl acetate and filter through a short plug of celite with additional ethyl acetate. Wash the organics with water, dry over magnesium sulfate, filter and evaporate. Purification by flash column chromatography yields 6-(4-fluorophenyl)pyridine-3-carboxylic acid methyl ester as a yellow solid. Dissolve the purified ester in tetrahydrofuran (0.25M) and add an equal volume of 1M sodium hydroxide. Stir vigorously at room temperature for 15 hours. Upon completion, acidify the reaction with conc. HCl and collect the white precipitate by filtration. Drying under vacuum yields 385 mg (37%) of the title compound. MS (m/e): 218.1 (MH+)

Workup

  1. customcollect the white precipitate
  2. filtrationby filtration
  3. customDrying under vacuum

Sources & evidence

ORD record
ord-b8cdfeb52b11472289bb9451a9088714
Source dataset
uspto-grants-2007_09
Patent number
US07265246B2

Reaction notes

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