Triethylamine → N-Methoxy-N-methyl-2-(trifluoromethyl)isonicotinamide

HRID 627485

Reaction equation

HRID 627485 reaction equation
[F:1][C:2]([F:13])([F:12])[C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][N:11]=1)[C:6](O)=[O:7].Cl.[CH3:15][NH:16][O:17][CH3:18].Cl.C(C(NCCCN(C)C)=N)C.CCN(CC)CC.[NH4+].[Cl-]>C(Cl)Cl>[CH3:18][O:17][N:16]([CH3:15])[C:6](=[O:7])[C:5]1[CH:9]=[CH:10][N:11]=[C:3]([C:2]([F:13])([F:12])[F:1])[CH:4]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 147614472-(Trifluoromethyl)pyridine-4-carboxylic acidHCID 178458058HCID 178458058, compound

Product 1

HCID 86716069N-Methoxy-N-methyl-2-(trifluoromethyl)isonicotinamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 2-(trifluoromethyl)isonicotinic acid (1.03 g, 5.39 mmol), N,O-dimethylhydroxylamine hydrochloride (0.800 g, 8.20 mmol), N′(ethylcarbonimidoyl)-N,N-dimethyl-1,3-propanediamine hydrochloride (EDCI, 1.35 g, 7.04 mmol) and CH2Cl2 was added Et3N (1.90 mL, 13.7 mmol), and the mixture immediately turned to clear. After stirring at room temperature overnight, NH4Cl (aqueous) was added. The mixture was stirred vigorously for a while, and white solid was filtered off. The organic layer was separated, and the aqueous layer was extracted with CH2Cl2. The combined organic phases were washed with brine, and the aqueous layer was back extracted with CH2Cl2. The organic phase was dried (Na2SO4), filtered, concentrated, and purified by flash column chromatography (40 g silica gel column, 40-70% EtOAc in heptanes) to give the title compound as a clear oil.

Workup

  1. stirringThe mixture was stirred vigorously for a while, and white solid
  2. filtrationwas filtered off
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with CH2Cl2
  5. washThe combined organic phases were washed with brine
  6. extractionthe aqueous layer was back extracted with CH2Cl2
  7. dry with materialThe organic phase was dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. custompurified by flash column chromatography (40 g silica gel column, 40-70% EtOAc in heptanes)

Sources & evidence

ORD record
ord-235aeff638e64e1f991c0d1977caebea
Source dataset
uspto-grants-2016_04
Patent number
US09309222B2

Linked notes

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