Potassium Phosphate, Tribasic → N-(4-tert-butyl-benzyl)-3-chloro-5-ethyl-N-[2-(3-fluoro-5-trifluoromethyl-phenyl)-ethyl]-benzamide

HRID 19811

Reaction equation

HRID 19811 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:32]=[C:33]([Cl:35])[CH:34]=1)[C:5]([N:7]([CH2:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]([CH3:31])([CH3:30])[CH3:29])=[CH:24][CH:23]=1)[CH2:8][CH2:9][C:10]1[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[C:12]([F:20])[CH:11]=1)=[O:6].[CH2:36](B(O)O)[CH3:37].P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>C1(C)C=CC=CC=1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:28]([C:25]1[CH:26]=[CH:27][C:22]([CH2:21][N:7]([CH2:8][CH2:9][C:10]2[CH:15]=[C:14]([C:16]([F:18])([F:17])[F:19])[CH:13]=[C:12]([F:20])[CH:11]=2)[C:5](=[O:6])[C:4]2[CH:3]=[C:2]([CH2:36][CH3:37])[CH:34]=[C:33]([Cl:35])[CH:32]=2)=[CH:23][CH:24]=1)([CH3:30])([CH3:29])[CH3:31]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 521157Ethylboronic acidHCID 866139943-bromo-N-(4-tert-butyl-benzyl)-5-chloro-N-[2-(3-fluoro-5-trifluoromethyl-phenyl)-ethyl]-benzamide

Product 1

HCID 68563631N-(4-tert-butyl-benzyl)-3-chloro-5-ethyl-N-[2-(3-fluoro-5-trifluoromethyl-phenyl)-ethyl]-benzamideYield 61.5%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent2×HCID 1140TolueneSolvent

Procedure

285 mg of 3-bromo-N-(4-tert-butyl-benzyl)-5-chloro-N-[2-(3-fluoro-5-trifluoromethyl-phenyl)-ethyl]-benzamide (0.6 mmol, Example B177), 44 mg of ethylboronic acid (1.75 mmol), 371 mg of tri-potassium phosphate (0.05 mmol), 14 mg of tricyclohexylphosphine and 6 mg of palladium acetate were suspended in 2.3 ml toluene and 0.1 ml water and stirred at 100° C. for 3.5 h under nitrogen. The reaction mixture was then cooled down to RT, diluted with 4 ml water and extracted twice with ethylacetate. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered off and concentrated under vacuo. The resulting residue was purified by flash column chromatography (Heptane/AcOEt:95/5) to yield 192 mg of a yellow solid. MS (ISP) 520.3 (M+H)+.

Workup

  1. extractionextracted twice with ethylacetate
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered off
  5. concentrationconcentrated under vacuo
  6. customThe resulting residue was purified by flash column chromatography (Heptane/AcOEt:95/5)

Sources & evidence

ORD record
ord-d21cfe3388354277955c93e18fae43b7
Source dataset
uspto-grants-2010_06
Patent number
US07745477B2

Linked notes

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