Hydrochloric Acid → 4-Amino-2-(trifluoromethyl)pyridine-3-carboxylic acid

HRID 1170897Notes

Reaction equation

HRID 1170897 reaction equation
[NH2:1][C:2]1[C:7]([C:8]([O:10]C)=[O:9])=[C:6]([C:12]([F:15])([F:14])[F:13])[N:5]=[CH:4][CH:3]=1.[OH-].[Li+].Cl.[Na+].[Cl-]>O1CCOCC1.CO.O>[NH2:1][C:2]1[C:7]([C:8]([OH:10])=[O:9])=[C:6]([C:12]([F:15])([F:13])[F:14])[N:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 5234Sodium ChlorideHCID 59553883Methyl 4-amino-2-(trifluoromethyl)nicotinate

Product 1

HCID 469351864-Amino-2-(trifluoromethyl)pyridine-3-carboxylic acidYield 95%

Reagents, catalysts & solvents 1

HCID 22592949Dioxane methanol waterSolvent

Conditions

Temperature
85 °C

Procedure

To a stirred solution of methyl 4-amino-2-(trifluoromethyl)nicotinate (1.97 g, 8.97 mmol) in dioxane/methanol/water (3:2:1 ratio by volume) is added lithium hydroxide (0.365 g, 15.2 mmol). The mixture was heated at 85° C. for 8 hours. The reaction mixture was cooled to room temperature and conc. HCl was added dropwise to adjust the pH to 2-3. Saturated NaCl solution was added. The aqueous layer is extracted with ethyl acetate (12×). The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to afford 1.75 g (95%) of 4-amino-2-(trifluoromethyl)nicotinic acid as a yellow solid. 1H NMR (400 MHz, CD3OD), 8.09 (d, 1H), 6.93 (d, 1H), LC/MS (M+1)=207.1.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionThe aqueous layer is extracted with ethyl acetate (12×)
  3. washThe organic layer is washed with water
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-38801805f1674356a658d270208bfb24
Source dataset
uspto-grants-2010_11
Patent number
US07829572B2

Reaction notes

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