Acetone → Benzamide

HRID 2261916Notes

Reaction equation

HRID 2261916 reaction equation
CN([C:7]1[CH:8]=[C:9]([CH:22]=[C:23](Br)[CH:24]=1)[C:10]([NH:12][C@@H](C1C=CC(F)=CC=1)C)=[O:11])S(C)(=O)=O.CC(C)=O.C(NC(C)C)(C)C.C[Si](C#C)(C)C>CCOC(C)=O.[Cu]I.[Pd].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.C(Cl)(Cl)Cl.[Pd].[Pd].O1CCOCC1>[C:10]([NH2:12])(=[O:11])[C:9]1[CH:22]=[CH:23][CH:24]=[CH:7][CH:8]=1

Participants

10

Reactant 4

HCID 180AcetoneHCID 7912DiisopropylamineHCID 66111TrimethylsilylacetyleneHCID 589900843-bromo-N-[(1R)-1-(4-fluorophenyl)ethyl]-5-[methyl(methylsulfonyl)amino]benzamide

Product 1

HCID 2331Benzamide

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 2734558Bis(tri-tert-butylphosphine)palladium(0)CatalystHCID 86615680Dipalladium chloroformCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 3-(N-methyl-N-(methylsulfonyl)amino)-5-bromo-N—((R)-1-(4-fluorophenyl)ethyl)benzamide (200 mg, 0.46 mmol), copper(I)iodide (3.6 mg, 0.019 mmol), bis(tri-t-butylphosphine) palladium (0) (14 mg, 0.028 mmol) and tris(dibenzylide acetone) dipalladium (0) chloroform adduct (14.2 mg, 0.014 mmol) in 0.5 mL degassed dioxane was added diisopropylamine (0.084 mL, 0.60 mmol) and (trimethylsilyl)acetylene (0.085 mL, 0.60 mmol). The reaction was stirred at rt overnight and then heated to 60° C. for an additional night. The mixture was diluted with EtOAc and filtered through celite. Concentration and flash chromatography (10-50% EtOAc/hexanes) gave 3-(N-methyl-N-(methylsulfonyl)amino)-N—((R)-1-(4-fluorophenyl)ethyl)-5-(2-trimethylsilyl)ethynyl)benzamide. 1H NMR (CDCl3) δ 7.77 (m, 1H), 7.67 (m, 1H), 7.61 (m, 1H), 7.35 (m, 2H), 7.05 (m, 2H), 6.28 (d, J=7.3 Hz, 1H), 5.29 (m, 1H), 3.33 (s, 3H), 2.86 (s, 3H), 1.60 (d, J=7.0 Hz, 3H), 0.26 (s, 9H).

Workup

  1. temperatureheated to 60° C. for an additional night
  2. filtrationfiltered through celite
  3. concentrationConcentration and flash chromatography (10-50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-7b841ceb63f14939821050a35721ec06
Source dataset
uspto-grants-2010_12
Patent number
US07847100B2

Reaction notes

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