Hydrochloric Acid → 2-(3,5-Difluoropyridin-2-yl)acetic acid

HRID 82286Notes

Reaction equation

HRID 82286 reaction equation
C([O:3][C:4](=[O:19])[CH:5]([C:11]1[C:16]([F:17])=[CH:15][C:14]([F:18])=[CH:13][N:12]=1)C(OCC)=O)C.O.[OH-].[Li+].Cl>C1COCC1.O>[F:17][C:16]1[C:11]([CH2:5][C:4]([OH:19])=[O:3])=[N:12][CH:13]=[C:14]([F:18])[CH:15]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 708176061,3-Diethyl 2-(3,5-difluoro-2-pyridinyl)propanedioate

Product 1

HCID 552678132-(3,5-Difluoropyridin-2-yl)acetic acidYield 53%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 2-(3,5-difluoro-pyridin-2-yl)-malonic acid diethyl ester (1 g, 3.56 mmol) (Preparation 264) in THF (15 mL) was added a solution of lithium hydroxide monohydrate (462 mg, 10.4 mmol) in water (4 mL) dropwise at 0° C. and the mixture heated to reflux for 2 hours. The reaction mixture was cooled to room temperature, acidified (pH ˜3) with 2N hydrochloric acid and extracted with 20% isopropanol-dichloromethane (5×20 mL). The combined organic layers were dried (Na2SO4) and evaporated in vacuo. The crude material was purified by column chromatography on silica gel (gradient of DCM: MeOH 100:0 to 95:5) to afford the title compound as a solid in 53% yield, 336 mg.

Workup

  1. temperaturethe mixture heated
  2. temperatureto reflux for 2 hours
  3. extractionextracted with 20% isopropanol-dichloromethane (5×20 mL)
  4. dry with materialThe combined organic layers were dried (Na2SO4)
  5. customevaporated in vacuo
  6. customThe crude material was purified by column chromatography on silica gel (gradient of DCM: MeOH 100:0 to 95:5)

Sources & evidence

ORD record
ord-dce74954527c4acbace125f724dbedab
Source dataset
uspto-grants-2014_09
Patent number
US08846698B2

Reaction notes

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