Citric Acid → HCID 68958430, compound

HRID 2191788Notes

Reaction equation

HRID 2191788 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:8][S:9]([CH3:12])(=[O:11])=[O:10])[CH:5]=[CH:6][CH:7]=1.C1(CNCC2CCCCC2)CCCCC1.[F:28][C:29]1[CH:50]=[CH:49][C:32]([NH:33][C:34]2[CH:46]=[C:45]([CH:47]=[CH2:48])[CH:44]=[CH:43][C:35]=2[C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])=[CH:31][CH:30]=1.F[B-](F)(F)F.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)(=O)C.CN(C)C(=O)C>[F:28][C:29]1[CH:50]=[CH:49][C:32]([NH:33][C:34]2[CH:46]=[C:45](/[CH:47]=[CH:48]/[C:2]3[CH:7]=[CH:6][CH:5]=[C:4]([NH:8][S:9]([CH3:12])(=[O:11])=[O:10])[CH:3]=3)[CH:44]=[CH:43][C:35]=2[C:36]([O:38][C:39]([CH3:42])([CH3:40])[CH3:41])=[O:37])=[CH:31][CH:30]=1

Participants

9

Reactant 5

HCID 311Citric AcidHCID 798932N-(3-bromophenyl)methanesulfonamide2×HCID 4594378Bis(cyclohexylmethyl)amine2×HCID 44558591Tri-t-butylphosphine fluoroborateHCID 68959213Tert-butyl 2-(4-fluoroanilino)-4-vinylbenzoate

Product 1

HCID 68958430HCID 68958430, compound

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
130 °C

Procedure

N-(3-Bromophenyl)methanesulfonamide 0.36 g, N,N-dicyclohexylmethylamine 0.41 mL and palladium acetate 5.4 mg were added to N,N-dimethylacetamide 3.0 mL solution of tert-butyl 2-(4-fluoroanilino)-4-vinylbenzoate 0.15 g at room temperature, and it was stirred at 130° C. for 4 hours. N-(3-bromophenyl)methanesulfonamide 0.12 g, N,N-dicyclohexylmethylamine 0.10 mL and (E)-di(μ-acetato)bis(o-(di-o-tolylphosphino)benzyl)dipalladium(II) 5.4 mg were added to it, and it was stirred at 130° C. for 2 hours. (E)-di(μ-acetato)bis(o-(di-o-tolylphosphino)benzyl)dipalladium(II) 11 mg and tri-tert-butylphosphine tetrafluoroborate 6.9 mg were added to it, and it was stirred at 130° C. for 8 hours. After the reaction mixture was cooled to room temperature, ethyl acetate and 10% citric acid aqueous solution were added to it. The organic layer was separated and collected, and the solvent was removed under reduced pressure after sequential washing with 10% citric acid aqueous solution, saturated sodium thiosulfate aqueous solution and saturated sodium chloride aqueous solution. The obtained residue was refined by silica gel column chromatography [Trikonex company, Flash Tube 2008, eluent; hexane:ethyl acetate=1:1] to give tert-butyl 2-(4-fluoroanilino)-4-((E)-2-(3-(methanesulfonamido)phenyl)vinyl)benzoate.

Workup

  1. stirringwas stirred at 130° C. for 2 hours
  2. stirringwas stirred at 130° C. for 8 hours
  3. temperatureAfter the reaction mixture was cooled to room temperature
  4. customThe organic layer was separated
  5. customcollected
  6. customthe solvent was removed under reduced pressure
  7. washafter sequential washing with 10% citric acid aqueous solution, saturated sodium thiosulfate aqueous solution and saturated sodium chloride aqueous solution

Sources & evidence

ORD record
ord-3bf20ab1ff9b45319682007ea44ec87d
Source dataset
uspto-grants-2012_12
Patent number
US08327467B2

Reaction notes

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