p-Fluorophenethylamine → 4-tert-butyl-2-chloro-N-[2-(4-fluoro-phenyl)-ethyl]-benzamide

HRID 855251Notes

Reaction equation

HRID 855251 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]1[CH:26]=[CH:25][C:24]([CH2:27][CH2:28][NH2:29])=[CH:23][CH:22]=1.CN([CH:33]=[O:34])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:33]([NH:29][CH2:28][CH2:27][C:24]2[CH:25]=[CH:26][C:21]([F:20])=[CH:22][CH:23]=2)=[O:34])=[C:7]([Cl:19])[CH:6]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 3

HCID 4653p-FluorophenethylamineHCID 6228DimethylformamideHCID 17859607Trifluoro-methanesulfonic acid 4-tert-butyl-2-chloro-phenyl ester

Product 1

HCID 693426474-tert-butyl-2-chloro-N-[2-(4-fluoro-phenyl)-ethyl]-benzamideYield 59%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
70 °C

Procedure

317 mg (1 mmol) of trifluoro-methanesulfonic acid 4-tert-butyl-2-chloro-phenyl ester and 281 mg (2 mmol) of 2-(4-fluoro-phenyl) ethyl amine were dissolved in 5 ml DMF. Under argon at rt 6.7 mg (0.03 mmol) of palladium acetate and 12.4 mg (0.03 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 198 mg (59%) of 4-tert-butyl-2-chloro-N-[2-(4-fluoro-phenyl)-ethyl]-benzamide as a white solid. 1H NMR (DMSO-d6, 300 MHz): δ 8.41 (t, 1H), 7.42 (s, 1H), 7.39 (d, 1H), 7.30 (d, 1H), 7.28 (t, 2H), 7.12 (t, 2H), 3.43 (q, 2H), 2.81 (t, 2H), 1.27 (s, 1H).

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-224f92cee91345d780ad350f92261fa6
Source dataset
uspto-grants-2007_08
Patent number
US07259183B2

Reaction notes

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