Hydrochloric Acid → 4-(4-Chloro-2-fluorophenyl)-6-methylnicotinic acid

HRID 1398433Notes

Reaction equation

HRID 1398433 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]=[C:10]([CH3:18])[CH:9]=2)=[C:4]([F:19])[CH:3]=1.[OH-].[Na+].Cl>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]=[C:10]([CH3:18])[CH:9]=2)=[C:4]([F:19])[CH:3]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 86695958Methyl 4-(4-chloro-2-fluorophenyl)-6-methylnicotinate

Product 1

HCID 867104124-(4-Chloro-2-fluorophenyl)-6-methylnicotinic acidYield 69.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a solution of Methyl 4-(4-chloro-2-fluorophenyl)-6-methylnicotinate (700 mg, 2.50 mmol) in MeOH (5 mL) was added NaOH (200 mg, 7.51 mmol) in water (5 mL). The reaction mixture was stirred at room temperature for 2 h. Then it was evaporated under reduced pressure and the residue obtained was adjusted to pH ˜3 by adding 1.5N HCl solution. The product was extracted with dichloromethane. The organic phase was dried over Na2SO4, and concentrated under reduced pressure to afford 4-(4-chloro-2-fluorophenyl)-6-methylnicotinic acid (500 mg, 1.730 mmol, 69% crude yield) as white solid. The material was carried forward without further purification. LC/MS (ESI) m/e 266.0 [(M+H)+, calcd for C13H10ClFNO2 266.0]; LC/MS retention time (Method I): tR=1.51 min.

Workup

  1. customThen it was evaporated under reduced pressure
  2. customthe residue obtained
  3. extractionThe product was extracted with dichloromethane
  4. dry with materialThe organic phase was dried over Na2SO4
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-4904e28e3cab42d5a2ba626687467ea0
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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