Sodium Hydroxide → 6-(2,2-Difluoropropoxy)-5-methylnicotinic acid

HRID 715429Notes

Reaction equation

HRID 715429 reaction equation
[F:1][C:2]([F:6])([CH3:5])[CH2:3][OH:4].CC(C)([O-])C.[K+].F[C:14]1[C:23]([CH3:24])=[CH:22][C:17]([C:18]([O:20]C)=[O:19])=[CH:16][N:15]=1.[OH-].[Na+]>CN(C=O)C.O.CO>[F:1][C:2]([F:6])([CH3:5])[CH2:3][O:4][C:14]1[C:23]([CH3:24])=[CH:22][C:17]([C:18]([OH:20])=[O:19])=[CH:16][N:15]=1

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 133948182,2-DifluoropropanolHCID 23665647Potassium tert-butoxideHCID 53419770Methyl 6-fluoro-5-methylpyridine-3-carboxylate

Product 1

HCID 898740426-(2,2-Difluoropropoxy)-5-methylnicotinic acidYield 87.3%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 2,2-difluoropropan-1-ol (1.13 g, 11.7 mmol) and potassium tert-butoxide (1.43 g, 12.8 mmol) in DMF (36 mL) is added methyl 6-fluoro-5-methylnicotinate (1.80 g, 10.6 mmol, Step-1 of Amine-36). After stirring at rt for 2 hours, MeOH (30 mL), water (30 mL), and 2 M aqueous sodium hydroxide solution (15 mL) are added to the mixture, and the mixture is stirred at rt for 2 hours. After evaporation of MeOH, the mixture is acidified by 2 M hydrochloric acid, and the precipitate is collected by filtration to give 2.14 g (87%) of the title compound as white solid.

Workup

  1. stirringthe mixture is stirred at rt for 2 hours
  2. customAfter evaporation of MeOH
  3. filtrationthe precipitate is collected by filtration

Sources & evidence

ORD record
ord-e050f30355b04a5ab878356d6bf70289
Source dataset
uspto-grants-2015_11
Patent number
US09187475B2

Reaction notes

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