Hydrochloric Acid → 5-Fluoro-2-(4-fluorophenoxy)nicotinic acid

HRID 1293160Notes

Reaction equation

HRID 1293160 reaction equation
[F:1][C:2]1[CH:3]=[N:4][C:5]([O:12][C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)=[C:6]([CH:11]=1)[C:7]([O:9]C)=[O:8].[OH-].[Na+].Cl>CO.O>[F:1][C:2]1[CH:3]=[N:4][C:5]([O:12][C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)=[C:6]([CH:11]=1)[C:7]([OH:9])=[O:8]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 57572291Methyl 5-fluoro-2-(4-fluorophenoxy)nicotinate

Product 1

HCID 575722785-Fluoro-2-(4-fluorophenoxy)nicotinic acidYield 91%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
40 °C

Procedure

To a stirred solution of methyl 5-fluoro-2-(4-fluorophenoxy)nicotinate (step 1, 2.63 g, 9.9 mmol) in methanol (50 mL) was added 2 N sodium hydroxide aqueous solution (10 mL). The reaction mixture was stirred at 40° C. for 3 h. After cooling, the pH value was adjusted to 4.0 by the addition of 2 N hydrochloric acid. The mixture was diluted with water (100 mL), and extracted with dichloromethane (100 mL×3). The combined organic layer was washed with brine (100 mL), dried (sodium sulfate), and concentrated to afford 2.26 g (91%) of the title compound as off white solids: 1H-NMR (CDCl3) δ 8.25 (1H, dd, J=7.5, 3.1 Hz), 8.16 (1H, d, J=3.1 Hz), 7.16–7.13 (4H, m); MS (ESI) m/z 252 (M+H)+.

Workup

  1. temperatureAfter cooling
  2. extractionextracted with dichloromethane (100 mL×3)
  3. washThe combined organic layer was washed with brine (100 mL)
  4. dry with materialdried (sodium sulfate)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-018ae53cbdc34858b07f567c7dd72569
Source dataset
uspto-grants-2007_07
Patent number
US07238714B2

Reaction notes

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