Sodium hydride → 5-Methyl-6-(3,3,3-trifluoropropoxy)nicotinic acid

HRID 715400Notes

Reaction equation

HRID 715400 reaction equation
[H-].[Na+].[F:3][C:4]([F:9])([F:8])[CH2:5][CH2:6][OH:7].F[C:11]1[C:20]([CH3:21])=[CH:19][C:14]([C:15]([O:17]C)=[O:16])=[CH:13][N:12]=1>C1COCC1.O>[CH3:21][C:20]1[C:11]([O:7][CH2:6][CH2:5][C:4]([F:9])([F:8])[F:3])=[N:12][CH:13]=[C:14]([CH:19]=1)[C:15]([OH:17])=[O:16]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 1375123,3,3-Trifluoro-1-propanolHCID 53419770Methyl 6-fluoro-5-methylpyridine-3-carboxylate

Product 1

HCID 898738585-Methyl-6-(3,3,3-trifluoropropoxy)nicotinic acidYield 100.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of sodium hydride (0.844 g, 21.1 mmol) in THF (10 mL), 3,3,3-trifluoropropan-1-ol (1.61 g, 14.1 mmol) in THF (10 mL) is added at 0° C., and stirred for 5 minutes. Then methyl 6-fluoro-5-methylnicotinate (1.19 g, 7.04 mmol, Step-1) in THF (10 mL) is added dropwise to the reaction mixture and stirred at rt for 2 hours. The reaction mixture is diluted with water (30 mL) and stirred overnight. After removal of THF, the mixture is acidified with 2 M hydrochloric acid (11 mL). The resulting white precipitate is collected by filtration and dried to give 1.76 g (>99% yield) of the title compound as white solid. This material is used for the next reaction (Step-3) without further purification.

Workup

  1. stirringstirred at rt for 2 hours
  2. stirringstirred overnight
  3. customAfter removal of THF
  4. filtrationThe resulting white precipitate is collected by filtration
  5. customdried

Sources & evidence

ORD record
ord-bb6f10934589407ca087ddfe05557ff1
Source dataset
uspto-grants-2015_11
Patent number
US09187475B2

Reaction notes

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