N-Methoxy-N-methyl-6-(4-trifluoromethyl-phenyl)-nicotinamide → 4,4,4-Trifluoro-1-[6-(4-trifluoromethyl-phenyl)-pyridin-3-yl]-butan-1-one

HRID 1669304Notes

Reaction equation

HRID 1669304 reaction equation
CON(C)[C:4](=[O:21])[C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=2)=[N:7][CH:6]=1.[F:23][C:24]([F:31])([F:30])[CH:25]([Mg]Br)[CH2:26]C>O1CCCC1>[F:23][C:24]([F:31])([F:30])[CH2:25][CH2:26][C:4]([C:5]1[CH:6]=[N:7][C:8]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=2)=[CH:9][CH:10]=1)=[O:21]

Participants

4

Reactant 2

HCID 86620355N-Methoxy-N-methyl-6-(4-trifluoromethyl-phenyl)-nicotinamideHCID 178456054HCID 178456054, compound

Product 1

HCID 860853424,4,4-Trifluoro-1-[6-(4-trifluoromethyl-phenyl)-pyridin-3-yl]-butan-1-oneYield 80.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

N-Methoxy-N-methyl-6-(4-trifluoromethyl-phenyl)-nicotinamide (2.0 g, 6.45 mmol) is suspended in anhydrous tetrahydrofuran (25.0 mL), and cooled to 0° C. with stirring under nitrogen. 1,1,1-Trifluoro-butyl magnesium bromide (11.3 mL, 1.14M in tetrahydrofuran, 12.9 mmol) is slowly added to the reaction over 1 h. The reaction is allowed to warm slowly to room temperature and monitored by TLC. Upon complete consumption of starting material, the reaction is carefully acidified with 1N hydrochloric acid, extracted with diethyl ether, washed, dried, and concentrated. The 4,4,4-Trifluoro-1-[6-(4-trifluoromethyl-phenyl)-pyridin-3-yl]-butan-1-one (1.80 g, 5.19 mmol) 80% yield, is used without further purification.

Workup

  1. temperatureto warm slowly to room temperature
  2. customUpon complete consumption of starting material
  3. extractionextracted with diethyl ether
  4. washwashed
  5. customdried
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-6362fe5d99a04a9caa8135b5e23f2cb7
Source dataset
uspto-grants-2011_08
Patent number
US07989457B2

Reaction notes

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