Sodium Hydroxide → 4-(4-Chloro-2-fluorophenyl)nicotinic acid

HRID 870914Notes

Reaction equation

HRID 870914 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([C:14]([O:16]C)=[O:15])=[CH:12][N:11]=[CH:10][CH:9]=2)=[C:4]([F:18])[CH:3]=1.[OH-].[Na+]>CO.O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([C:14]([OH:16])=[O:15])=[CH:12][N:11]=[CH:10][CH:9]=2)=[C:4]([F:18])[CH:3]=1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 86695906Methyl 4-(4-chloro-2-fluorophenyl)nicotinate

Product 1

HCID 866959074-(4-Chloro-2-fluorophenyl)nicotinic acidYield 31.7%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a solution of methyl 4-(4-chloro-2-fluorophenyl)nicotinate (1 g, 3.76 mmol) in MeOH (10 mL) and water (10 mL) was added NaOH (0.602 g, 15.06 mmol) and the solution stirred at room temperature for 2 h. The volatile organic solvent was evaporated under reduced pressure. The reaction mixture was cooled to 0° C. and acidified with 50% aqueous HCl. The precipitated so formed was collected by vacuum filtration to yield 4-(4-chloro-2-fluorophenyl)nicotinic acid (0.3 g, 1.192 mmol, 30% crude yield) as an off-white solid which was carried directly into the next step. 1H NMR (400 MHz, CD3OD) δ 9.12 (s, 1H), 8.78 (d, J=5.20 Hz, 1H), 7.29-7.48 (m, 4H).

Workup

  1. customThe volatile organic solvent was evaporated under reduced pressure
  2. temperatureThe reaction mixture was cooled to 0° C.
  3. customThe precipitated so
  4. customformed
  5. filtrationwas collected by vacuum filtration

Sources & evidence

ORD record
ord-ca8db6d8965443d0b7b9ed32ed0f7961
Source dataset
uspto-grants-2015_03
Patent number
US08969564B2

Reaction notes

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