Potassium Acetate → 5-cyano-2-methoxy-N-[2-(3',4',5'-trifluoro-3-methoxymethoxybiphenyl-4-yl)ethyl]benzenesulfonamide

HRID 229587Notes

Reaction equation

HRID 229587 reaction equation
FC(F)(F)S(O[C:7]1[CH:12]=[CH:11][C:10]([CH2:13][CH2:14][NH:15][S:16]([C:19]2[CH:24]=[C:23]([C:25]#[N:26])[CH:22]=[CH:21][C:20]=2[O:27][CH3:28])(=[O:18])=[O:17])=[C:9]([O:29][CH2:30][O:31][CH3:32])[CH:8]=1)(=O)=O.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].Br[C:59]1[CH:64]=[C:63]([F:65])[C:62]([F:66])=[C:61]([F:67])[CH:60]=1.[PH2](=O)[O-].[K+]>O.C(OCC)(=O)C.O1CCOCC1>[C:25]([C:23]1[CH:22]=[CH:21][C:20]([O:27][CH3:28])=[C:19]([S:16]([NH:15][CH2:14][CH2:13][C:10]2[CH:11]=[CH:12][C:7]([C:59]3[CH:64]=[C:63]([F:65])[C:62]([F:66])=[C:61]([F:67])[CH:60]=3)=[CH:8][C:9]=2[O:29][CH2:30][O:31][CH3:32])(=[O:18])=[O:17])[CH:24]=1)#[N:26]

Participants

9

Reactant 5

HCID 517044Potassium AcetateHCID 6114091-Bromo-3,4,5-trifluorobenzeneHCID 2733548Bis(pinacolato)diboraneHCID 184569554-[2-(5-Cyano-2-methoxybenzenesulfonylamino)ethyl]-3-methoxymethoxyphenyl trifluoromethanesulfonateHCID 178527018HCID 178527018, compound

Product 1

HCID 184569645-cyano-2-methoxy-N-[2-(3',4',5'-trifluoro-3-methoxymethoxybiphenyl-4-yl)ethyl]benzenesulfonamideYield 104.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
80 °C

Procedure

A mixture of 10.0 g of 4-[2-(5-cyano-2-methoxybenzenesulfonylamino)ethyl]-3-methoxymethoxyphenyl trifluoromethanesulfonate, 5.33 g of bis(pinacolato)diboron, 467 mg of 1,1′-bis(diphenylphosphino)ferrocenepalladium(II) dichloride dichloromethane complex, 317 mg of 1,1′-bis(diphenylphosphino)ferrocenepalladium(II), 5.61 g of potassium acetate, and 113 mL of 1,4-dioxane was stirred under an argon atmosphere at 80° C. for 15 hours. To the reaction mixture were added 4.02 g of 1-bromo-3,4,5-trifluorobenzene, 467 mg of 1,1′-bis(diphenylphosphino)ferrocenepalladium(II) dichloride dichloromethane complex, 12.14 g of potassium phosphinate, and 40 mL of 1,4-dioxane. The mixture was stirred under argon atmosphere at 80° C. for 24 hours, and ethyl acetate and water were added to the reaction mixture. The organic layer was separated, washed with water, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography on aminopropylated silica gel (eluent: ethyl acetate-hexane) to give 10.09 g of 5-cyano-2-methoxy-N-[2-(3′,4′,5′-trifluoro-3-methoxymethoxybiphenyl-4-yl)ethyl]benzenesulfonamide.

Workup

  1. stirringThe mixture was stirred under argon atmosphere at 80° C. for 24 hours
  2. customThe organic layer was separated
  3. washwashed with water
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customthe residue was purified by column chromatography on aminopropylated silica gel (eluent: ethyl acetate-hexane)

Sources & evidence

ORD record
ord-56356db5526d407ea840a04b148809f6
Source dataset
uspto-grants-2009_07
Patent number
US07563822B2

Reaction notes

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