3-(Trifluoromethyl)aniline → 4-Bromo-N-(3-(trifluoromethyl)phenyl)picolinamide

HRID 1052038Notes

Reaction equation

HRID 1052038 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]([OH:10])=O)[CH:3]=1.CN1CCOCC1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.[F:42][C:43]([F:52])([F:51])[C:44]1[CH:45]=[C:46]([CH:48]=[CH:49][CH:50]=1)[NH2:47]>CN(C)C=O.ClCCl>[Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]([NH:47][C:46]2[CH:48]=[CH:49][CH:50]=[C:44]([C:43]([F:42])([F:51])[F:52])[CH:45]=2)=[O:10])[CH:3]=1

Participants

7

Reactant 4

HCID 73753-(Trifluoromethyl)anilineHCID 79724-MethylmorpholineHCID 7351504-Bromopyridine-2-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 866958504-Bromo-N-(3-(trifluoromethyl)phenyl)picolinamideYield 76%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a suspension of 4-bromo-pyridine-2-carboxylic acid (1.00 g, 5.00 mmol) in dimethylformamide (5 mL) was added 1-methylmorpholine (1.1 mL, 10 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyl-uronium hexafluorophosphate (HATU) (2.37 g, 6.23 mmol). The mixture became an orange solution after 10 minutes. 3-Trifluoromethylaniline (0.5 mL, 5.5 mmol) was added and the solution was stirred at room temperature for 21 hours. The dimethylformamide was evaporated in vacuo and the residue was triturated with water. The resulting solid was filtered and washed twice with water and then vacuum dried at 40° C. to give a crude residue. Chromatography on silica gel (40 g), sample applied in dichloromethane and eluted with hexanes:ethyl acetate (1:1) gave the title compound (1.306 g, 76%).

Workup

  1. customafter 10 minutes
  2. customThe dimethylformamide was evaporated in vacuo
  3. customthe residue was triturated with water
  4. filtrationThe resulting solid was filtered
  5. washwashed twice with water
  6. customvacuum dried at 40° C.
  7. customto give a crude residue
  8. washeluted with hexanes:ethyl acetate (1:1)

Sources & evidence

ORD record
ord-413b511ec26947cbbe591668f817231d
Source dataset
uspto-grants-2016_07
Patent number
US09388176B2

Reaction notes

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