Dimethylformamide → 4-tert-butyl-2-chloro-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide

HRID 855253Notes

Reaction equation

HRID 855253 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8](OS(C(F)(F)F)(=O)=O)=[C:7]([Cl: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]([Cl:19])[CH:6]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 104223Phenethylamine, m-trifluoromethyl-HCID 17859607Trifluoro-methanesulfonic acid 4-tert-butyl-2-chloro-phenyl ester

Product 1

HCID 693465104-tert-butyl-2-chloro-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamideYield 39%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
70 °C

Procedure

633 mg (2 mmol) of trifluoro-methanesulfonic acid 4-tert-butyl-2-chloro-phenyl ester (prepared as described in example S80) and 416 mg (2.2 mmol) of 2-(3-trifluoromethyl-phenyl) ethyl amine were dissolved in 10 ml DMF. Under argon at rt 13.4 mg (0.06 mmol) of palladium acetate and 24.8 mg (0.06 mmol) of dppp were added. The reaction mixture was evacuated and charged with carbon monoxide gas three times. The reaction mixture was heated to 70° 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 (45 g silica gel, heptane/EtOAc 7:3) to yield 298 mg (39%) of 4-tert-butyl-2-chloro-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide as a light yellow solid. 1H NMR (DMSO-d6, 300 MHz): δ 8.43 (t, 1H), 7.61-7.55 (m, 4H), 7.41 (s, 1H), 7.36 (d, 2H), 7.22 (d, 1H), 3.50 (q, 2H), 2.93 (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 (45 g silica gel, heptane/EtOAc 7:3)

Sources & evidence

ORD record
ord-d495b0f6db994c199514bea746bbca6c
Source dataset
uspto-grants-2007_08
Patent number
US07259183B2

Reaction notes

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