Sodium Hydroxide → 4-(4-Chloro-2-fluorophenyl)-2-methylpyridine-3-carboxylic acid

HRID 1398336Notes

Reaction equation

HRID 1398336 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])=[C:12]([CH3:18])[N:11]=[CH:10][CH:9]=2)=[C:4]([F:19])[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])=[C:12]([CH3:18])[N:11]=[CH:10][CH:9]=2)=[C:4]([F:19])[CH:3]=1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 86710334Methyl 4-(4-chloro-2-fluorophenyl)-2-methylnicotinate

Product 1

HCID 867103354-(4-Chloro-2-fluorophenyl)-2-methylpyridine-3-carboxylic acidYield 79%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a solution of methyl 4-(4-chloro-2-fluorophenyl)-2-methylnicotinate (40 mg, 0.143 mmol) in MeOH (2 mL) and water (3 mL) was added NaOH (11.44 mg, 0.286 mmol) and the reaction mixture was stirred at RT for 14 h. The reaction mixture was concentrated under reduced pressure and acidified with 1.5N HCl the extracted with ethyl acetate (5 mL). The organic layer was washed with saturated NaHCO3 (2×10 mL) and water (10 mL); dried over Na2SO4 and concentrated under reduced pressure to afford crude 4-(4-chloro-2-fluorophenyl)-2-methylnicotinic acid (30 mg, 0.113 mmol, 79% yield) as brown solid. This was taken into the next step without further purification. LC/MS, (ESI) m/z 266.1 [(M+H)+, calcd for C13H10ClFNO2. 266.0]; LC/MS retention time (method D): tR=0.64 min.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. extractionextracted with ethyl acetate (5 mL)
  3. washThe organic layer was washed with saturated NaHCO3 (2×10 mL) and water (10 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-43eb63e365c242d9abf2d2fc2ffd668c
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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