Dimethylformamide → HCID 69347256, compound

HRID 855259Notes

Reaction equation

HRID 855259 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8](OS(C(F)(F)F)(=O)=O)=[C:7]([F:19])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[F:20][C:21]([F:32])([F:31])[C:22]1[CH:23]=[C:24]([CH2:28][CH2:29][NH2:30])[CH:25]=[CH:26][CH:27]=1.CN([CH:36]=[O:37])C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1C=CC(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:36]([NH:30][CH2:29][CH2:28][C:24]2[CH:25]=[CH:26][CH:27]=[C:22]([C:21]([F:31])([F:32])[F:20])[CH:23]=2)=[O:37])=[C:7]([F:19])[CH:6]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 104223Phenethylamine, m-trifluoromethyl-HCID 86603038HCID 86603038, compound

Product 1

HCID 69347256HCID 69347256, compoundYield 63%

Reagents, catalysts & solvents 2

HCID 812191,3-Bis(diphenylphosphino)propaneCatalystHCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
80 °C

Procedure

880 mg (2.93 mmol) of trifluoro-methanesulfonic acid 4-tert-butyl-2-fluoro-phenyl ester and 1.13 g (5.86 mmol) of 2-(3-trifluoromethyl-phenyl) ethyl amine were dissolved in 15 ml DMF. Under argon at rt 19.7 mg (0.0.88 mmol) of palladium acetate and 36.2 mg (0.088 mmol) of dppp were added. The reaction mixture was evacuated and charged with carbon monoxide gas three times. The reaction mixture was heated to 80° C. under a carbon monoxide atmosphere for 1 h. Water was added and the reaction mixture was extracted twice with EtOAc. The combined organic layers were washed with 1N aqueous HCl solution, once with saturated aqueous NaCl solution, dried over sodium sulfate, filtered and the solvent was evaporated. The residue was purified by column chromatography (60 g silica gel; heptane/EtOAc 7:3) to yield 676 mg (63%) of 4-tert-butyl-2-fluoro-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide as a yellow viscous oil. 1H NMR (DMSO-d6, 300 MHz): δ 8.28 (t, 1H), 7.60-7.55 (m, 4H), 7.47 (t, 1H), 7.28-7.22 (m, 2H), 3.51 (q, 2H), 2.94 (t, 2H), 1.27 (s, 9H).

Workup

  1. customThe reaction mixture was evacuated
  2. additioncharged with carbon monoxide gas three times
  3. additionWater was added
  4. extractionthe reaction mixture was extracted twice with EtOAc
  5. washThe combined organic layers were washed with 1N aqueous HCl solution, once with saturated aqueous NaCl solution
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customthe solvent was evaporated
  9. customThe residue was purified by column chromatography (60 g silica gel; heptane/EtOAc 7:3)

Sources & evidence

ORD record
ord-4031820964064f7fbc3f448128a2ddd0
Source dataset
uspto-grants-2007_08
Patent number
US07259183B2

Reaction notes

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