Water → 6-[Methyl(3,3,3-trifluoropropyl)carbamoyl]nicotinic acid

HRID 1099439Notes

Reaction equation

HRID 1099439 reaction equation
[F:1][C:2]([F:19])([F:18])[CH2:3][CH2:4][NH:5][C:6]([C:8]1[CH:17]=[CH:16][C:11]([C:12]([O:14]C)=[O:13])=[CH:10][N:9]=1)=[O:7].[H-].[Na+].[CH3:22]I.O>CN(C)C=O>[CH3:22][N:5]([CH2:4][CH2:3][C:2]([F:19])([F:18])[F:1])[C:6]([C:8]1[CH:17]=[CH:16][C:11]([C:12]([OH:14])=[O:13])=[CH:10][N:9]=1)=[O:7]

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 59354919HCID 59354919, compound

Product 1

HCID 593549166-[Methyl(3,3,3-trifluoropropyl)carbamoyl]nicotinic acidYield 47.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of methyl 6-[(3,3,3-trifluoropropyl)carbamoyl]nicotinate (2.4 g, 8.6 mmol) in N,N-dimethylformamide (10 mL) was added sodium hydride (60% suspension in mineral oil) (1.3 g). The reaction mixture was stirred at ambient temperature for 1 h. Methyl iodide (3.42 g, 5.0 mL, 24.1 mmol) was added and the reaction mixture was stirred over night and then added water (20 mL). The reaction mixture was stirred for another 30 min and then extracted with ethyl acetate (2×50 mL). The aqueous layer was acidified with citric acid and the formed precipitate was filtered off and dried in vacuum oven to yield 1.12 g (47%) of the title compound; 1H NMR (400 MHz, CDCl3) δ ppm 9.26 (d, 1 H), 8.49 (d, 1 H), 7.78-7.91 (dd, 1 H), 3.80 (t, 1 H), 3.61-3.73 (m, 1 H), 3.16 (d, 3 H), 2.46-2.76 (m, 2 H); MS (ESI) m/z 277[M+H+].

Workup

  1. stirringthe reaction mixture was stirred over night
  2. stirringThe reaction mixture was stirred for another 30 min
  3. extractionextracted with ethyl acetate (2×50 mL)
  4. filtrationthe formed precipitate was filtered off
  5. customdried in vacuum oven

Sources & evidence

ORD record
ord-73b45ad9e93b4a22a8e546b3768918bd
Source dataset
uspto-grants-2012_03
Patent number
US08143408B2

Reaction notes

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