Methanamine, N-methoxy-, hydrochloride (1:1) → N-Methoxy-N-methyl-6-(4-trifluoromethyl-phenyl)-nicotinamide

HRID 1669303Notes

Reaction equation

HRID 1669303 reaction equation
CO[C:3](=[O:20])[C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][CH:11]=2)=[N:6][CH:5]=1.Cl.[CH3:22][NH:23][O:24][CH3:25].C([Mg]Cl)(C)C>O1CCCC1>[CH3:25][O:24][N:23]([CH3:22])[C:3](=[O:20])[C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:11]=[CH:12][C:13]([C:16]([F:17])([F:18])[F:19])=[CH:14][CH:15]=2)=[N:6][CH:5]=1

Participants

5

Reactant 3

HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 21936350Methyl 6-(4-(trifluoromethyl)phenyl)nicotinateHCID 178418918HCID 178418918, compound

Product 1

HCID 86620355N-Methoxy-N-methyl-6-(4-trifluoromethyl-phenyl)-nicotinamideYield 99.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-30 °C

Procedure

6-(4-Trifluoromethyl-phenyl)-nicotinic acid methyl ester (20 g, 71.2 mmol) is dissolved into anhydrous tetrahydrofuran (TVF) (300 mL) and then cooled to −30° C. while stirring under nitrogen. N,O-dimethylhydroxylamine hydrochloride (10.4 g, 107 mmol) is then added to the solution in one portion. Isopropyl magnesium chloride (107 mL, 2M soln. in THF, 252 mmol) is slowly added to the cooled suspension over 2 h. After complete consumption of starting material, 30% solution of ammonium chloride is added with stirring. The reaction is diluted with diethyl ether, water, and extracted. The organic layer is collected and washed with cold water (2×) and brine. The solution is then dried over anhydrous sodium sulfate, filtered, and concentrated. The N-Methoxy-N-methyl-6-(4-trifluoromethyl-phenyl)-nicotinamide (22 g, 71 mmol) is obtained in purified form after flash column chromatography.

Workup

  1. customAfter complete consumption of starting material, 30% solution of ammonium chloride
  2. additionis added
  3. stirringwith stirring
  4. additionThe reaction is diluted with diethyl ether, water
  5. extractionextracted
  6. customThe organic layer is collected
  7. washwashed with cold water (2×) and brine
  8. dry with materialThe solution is then dried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-32170527dd65416fa7097f5a8e92f335
Source dataset
uspto-grants-2011_08
Patent number
US07989457B2

Reaction notes

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