Sodium Hydroxide → 6-(2,6-Difluorophenyl)pyridine-3-carboxylic acid

HRID 2224726Notes

Reaction equation

HRID 2224726 reaction equation
C([O:3][C:4]([C:6]1[CH:7]=[N:8][C:9]([C:12]2[C:17]([F:18])=[CH:16][CH:15]=[CH:14][C:13]=2[F:19])=[CH:10][CH:11]=1)=[O:5])C.[OH-].[Na+]>CO>[F:19][C:13]1[CH:14]=[CH:15][CH:16]=[C:17]([F:18])[C:12]=1[C:9]1[N:8]=[CH:7][C:6]([C:4]([OH:5])=[O:3])=[CH:11][CH:10]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 69129633Ethyl 6-(2,6-difluorophenyl)-3-pyridinecarboxylate

Product 1

HCID 532230666-(2,6-Difluorophenyl)pyridine-3-carboxylic acidYield 63%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Combine the mixture as obtained above (0.225 g, 1.04 mmol) with hexamethylditin (0.375 g, 1.15 mmol), Pd(OAc)2 (21 mg, 0.09 mmol), and triphenylphosphine (25 mg, 0.09 mmol) in toluene (5 mL). Purge with N2 and stir at 80° C. for 18 hours. Cool reaction to room temperature. Add a solution of 1-bromo-2,6-difluorobenzene (250 mg, 1.29 mmol) in toluene (1 mL) followed by Pd(OAc)2 (21 mg, 0.09 mmol) and triphenylphosphine (25 mg, 0.09 mmol). Purge with N2 and stir at 80° C. for an additional 18 hours. Cool reaction to room temperature. Evaporate the solvent and purify by column chromatography (silica, 10% ethyl acetate in hexane) to give 50 mg (20% yield) of 6-(2,6-difluorophenyl)pyridine-3-carboxylic acid ethyl ester. Hydrolyze the ester with 1N sodium hydroxide solution (0.22 mL, 0.22 mmol) in methanol (3 mL) at room temperature for 3 days. Remove the volatiles under vacuum and combine the residue with 1N hydrochloric acid solution. Collect the white solid by filtration, wash with water, and dry under vacuum to give 30 mg (63% yield) of the title compound. MS (ES): m/z 235.9 (M+H).

Workup

  1. customat room temperature
  2. customfor 3 days
  3. customRemove the volatiles under vacuum
  4. customCollect the white solid
  5. filtrationby filtration
  6. washwash with water
  7. customdry under vacuum

Sources & evidence

ORD record
ord-b2b54236a28a46e6b247879e37291c53
Source dataset
uspto-grants-2008_05
Patent number
US07378447B2

Reaction notes

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