Lithium Hydroxide → 2-(Difluoromethyl)-5-(isobutyramidomethyl)nicotinic acid

HRID 1469797Notes

Reaction equation

HRID 1469797 reaction equation
[F:1][CH:2]([F:21])[C:3]1[N:13]=[CH:12][C:11]([CH2:14][NH:15][C:16](=[O:20])[CH:17]([CH3:19])[CH3:18])=[CH:10][C:4]=1[C:5]([O:7]CC)=[O:6].[Li+].[OH-]>O1CCOCC1.O>[F:21][CH:2]([F:1])[C:3]1[N:13]=[CH:12][C:11]([CH2:14][NH:15][C:16](=[O:20])[CH:17]([CH3:19])[CH3:18])=[CH:10][C:4]=1[C:5]([OH:7])=[O:6]

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 71059744Ethyl 2-(difluoromethyl)-5-(isobutyramidomethyl)nicotinate

Product 1

HCID 710598402-(Difluoromethyl)-5-(isobutyramidomethyl)nicotinic acidYield 83.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of ethyl 2-(difluoromethyl)-5-(isobutyramidomethyl)nicotinate (200 mg, 0.66 mmol) in 1,4-Dioxane was added a solution of LiOH (70 mg, 1.66 mmol) in H2O (1 mL) and the reaction mixture was stirred at rt for 1 h. Then the reaction mixture was quenched with 1N HCl and the precipitated solid was filtered and dried to afford 150 mg of the title product. 1H NMR (300 MHz, DMSO d6): δ 13.98 (br s, 1H), 8.72 (s, 1H), 8.45 (t, 1H), 8.17 (s, 1H), 7.67-7.32 (t, J=54 Hz, 1H), 4.39-4.37 (d, J=5.7 Hz, 2H), 2.43 (m, 1H), 1.04-1.02 (d, J=6.6 Hz, 6H).

Workup

  1. customThen the reaction mixture was quenched with 1N HCl
  2. filtrationthe precipitated solid was filtered
  3. customdried

Sources & evidence

ORD record
ord-899338ff0e1a4ce2b13d6d88e2de94ca
Source dataset
uspto-grants-2015_04
Patent number
US09006257B2

Reaction notes

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