Sodium Hydroxide → 5-fluoropyridine-2-carboxylic Acid

HRID 130829

Reaction equation

HRID 130829 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([O:10]CC)=[O:9])=[N:6][CH:7]=1.[OH-].[Na+]>C1COCC1.CO>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([OH:10])=[O:9])=[N:6][CH:7]=1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 10986675Ethyl 5-fluoropyridine-2-carboxylate

Product 1

HCID 27628765-fluoropyridine-2-carboxylic AcidYield 100%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Dissolve ethyl 5-fluoropyridine-2-carboxylate (4.60 g, 27.2 mmol) in THF (34 mL) and methanol (34 mL). Add 1.0 N NaOH (32.6, 32.6 mmol) and stir at room temperature for 1.3 hours. Concentrate the reaction mixture. Then add 1.0 N HCl (32.6 mL), stir and concentrate. Take the solid up in 20% methanol, 3% AcOH and 77% dichloromethane and filter through a silica plus. Wash the plug with the solvent listed above until all of the product elutes off to give the title compound (3.8 g, 100%): MS ES+ 142.03 (M+H)+, HRMS calcd for C6H5NO2F 142.0304 (M+H)+, found 142.0306, time 0.46 min, 0.51; HPLC [YMC-Pack Pro C-18 (150×4.6 mm, S-5 microm), 0.1% TFA/acetonitrile in 0.1% TFA/water at 1.0 mL/min, 5-95% over 19 min], tR=6.3 min, 100% purity.

Workup

  1. concentrationConcentrate the reaction mixture
  2. additionThen add 1.0 N HCl (32.6 mL)
  3. stirringstir
  4. concentrationconcentrate
  5. filtrationfilter through a silica plus
  6. washWash the plug with the solvent

Sources & evidence

ORD record
ord-c7f9512cafba417c8135951e27968ea7
Source dataset
uspto-grants-2008_06
Patent number
US07381719B2

Linked notes

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