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

HRID 855255Notes

Reaction equation

HRID 855255 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].Cl.[F:21][C:22]([F:34])([F:33])[O:23][C:24]1[CH:25]=[C:26]([CH2:30][CH2:31][NH2:32])[CH:27]=[CH:28][CH:29]=1.C(N(CC)CC)C.C1C=CC(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CN([CH:74]=[O:75])C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:74]([NH:32][CH2:31][CH2:30][C:26]2[CH:27]=[CH:28][CH:29]=[C:24]([O:23][C:22]([F:33])([F:34])[F:21])[CH:25]=2)=[O:75])=[C:7]([Cl:19])[CH:6]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 812191,3-Bis(diphenylphosphino)propaneHCID 17859607Trifluoro-methanesulfonic acid 4-tert-butyl-2-chloro-phenyl esterHCID 574385032-[3-(Trifluoromethoxy)phenyl]ethan-1-amine hydrochloride

Product 1

HCID 695134924-tert-butyl-2-chloro-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]-benzamideYield 10%

Reagents, catalysts & solvents 1

HCID 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), 532 mg (2.2 mmol) of 2-(3-trifluoromethoxy-phenyl) ethyl amine hydrochloride and 223 mg (2.2 mmol) of triethyl 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 (60 g silica gel; heptane/EtOAc 7:3) to yield 82 mg (10%) of 4-tert-butyl-2-chloro-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]-benzamide as a light yellow solid. 1H NMR (DMSO-d6, 300 MHz): δ 8.43 (t, 1H), 7.44-7.41 (m, 2H), 7.37 (d, 1H), 7.31 (d, 1H), 7.26-7.21 (m, 3H), 3.48 (q, 2H), 2.88 (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-6507f53cfde240c2bb4ba844f677dde9
Source dataset
uspto-grants-2007_08
Patent number
US07259183B2

Reaction notes

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