Hydrochloric Acid → 6-(4,4-Difluoropiperidin-1-yl)-5-methylnicotinic acid

HRID 715472Notes

Reaction equation

HRID 715472 reaction equation
F[C:2]1[C:11]([CH3:12])=[CH:10][C:5]([C:6]([O:8]C)=[O:7])=[CH:4][N:3]=1.Cl.[F:14][C:15]1([F:21])[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1.C(=O)([O-])[O-].[Cs+].[Cs+].[OH-].[Na+].Cl>CN(C=O)C.CO>[F:14][C:15]1([F:21])[CH2:20][CH2:19][N:18]([C:2]2[C:11]([CH3:12])=[CH:10][C:5]([C:6]([OH:8])=[O:7])=[CH:4][N:3]=2)[CH2:17][CH2:16]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 14798Sodium HydroxideHCID 27583514,4-Difluoropiperidine hydrochlorideHCID 53419770Methyl 6-fluoro-5-methylpyridine-3-carboxylate

Product 1

HCID 898745496-(4,4-Difluoropiperidin-1-yl)-5-methylnicotinic acidYield 39%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of methyl 6-fluoro-5-methylnicotinate (2.00 g, 11.8 mmol), 4,4-difluoropiperidine hydrochloride (4.66 g, 29.6 mmol), and cesium carbonate (13.5 g, 41.4 mmol) in DMF is stirred at 120° C. for 16 hours. After cooling to rt, 1 M aqueous sodium hydroxide solution (50 mL) and MeOH (50 mL) are added to the resulting mixture. After stirring at 60° C. for 3 hours, the mixture is acidified by 2 M hydrochloric acid (pH is around 4), and MeOH is removed in vacuo. The formed white precipitate is collected by filtration to give 1.17 g (39%) of the title compound as white solid.

Workup

  1. temperatureAfter cooling to rt
  2. stirringAfter stirring at 60° C. for 3 hours
  3. customis removed in vacuo
  4. filtrationThe formed white precipitate is collected by filtration

Sources & evidence

ORD record
ord-3d58f5c9351d42d8bc5596f752b95df5
Source dataset
uspto-grants-2015_11
Patent number
US09187475B2

Reaction notes

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