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1,4-Dioxane → 4-tert-butyl-N-{5-(4-methylphenyl)-6-(2-phenoxyethoxy)pyrimidin-4-yl}benzenesulfonamide

HRID 2279
Notes
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Reaction equation

HRID 2279 reaction equation
Br[C:2]1[CH:38]=[CH:37][C:5]([O:6][CH2:7][CH2:8][O:9][C:10]2[N:15]=[CH:14][N:13]=[C:12]([NH:16][S:17]([C:20]3[CH:25]=[CH:24][C:23]([C:26]([CH3:29])([CH3:28])[CH3:27])=[CH:22][CH:21]=3)(=[O:19])=[O:18])[C:11]=2[C:30]2[CH:35]=[CH:34][C:33]([CH3:36])=[CH:32][CH:31]=2)=[CH:4][CH:3]=1.[CH2:39]([O:41]C([Sn](CCCC)(CCCC)CCCC)=C)[CH3:40].O1C[CH2:61][O:60][CH2:59][CH2:58]1.[F-].[K+]>C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[C:26]([C:23]1[CH:22]=[CH:21][C:20]([S:17]([NH:16][C:12]2[C:11]([C:30]3[CH:35]=[CH:34][C:33]([CH3:36])=[CH:32][CH:31]=3)=[C:10]([O:9][CH2:8][CH2:7][O:6][C:5]3[CH:4]=[CH:3][CH:2]=[CH:38][CH:37]=3)[N:15]=[CH:14][N:13]=2)(=[O:19])=[O:18])=[CH:25][CH:24]=1)([CH3:29])([CH3:27])[CH3:28].[C:39]([C:2]1[CH:38]=[CH:37][C:5]([O:6][CH2:7][CH2:8][O:9][C:10]2[N:15]=[CH:14][N:13]=[C:12]([NH:16][S:17]([C:20]3[CH:25]=[CH:24][C:23]([C:26]([CH3:28])([CH3:27])[CH3:29])=[CH:22][CH:21]=3)(=[O:19])=[O:18])[C:11]=2[C:30]2[CH:35]=[CH:34][C:33]([CH3:36])=[CH:32][CH:31]=2)=[CH:4][CH:3]=1)(=[O:41])[CH3:40].[C:26]([C:23]1[CH:24]=[CH:25][C:20]([S:17]([NH:16][C:12]2[C:11]([C:30]3[CH:35]=[CH:34][C:33]([CH3:36])=[CH:32][CH:31]=3)=[C:10]([O:9][CH2:8][CH2:7][O:6][C:5]3[CH:37]=[CH:38][C:2]([C:61]([O:60][CH2:59][CH3:58])=[O:41])=[CH:3][CH:4]=3)[N:15]=[CH:14][N:13]=2)(=[O:19])=[O:18])=[CH:21][CH:22]=1)([CH3:29])([CH3:28])[CH3:27]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

9

Reactant 4

HCID 312751,4-DioxaneHCID 522689Potassium FluorideHCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 19689478N-[6-{2-(4-bromophenoxy)ethoxy}-5-(4-methylphenyl)pyrimidin-4-yl]-4-tert-butylbenzenesulfonamide

Product 3

HCID 196894604-tert-butyl-N-{5-(4-methylphenyl)-6-(2-phenoxyethoxy)pyrimidin-4-yl}benzenesulfonamide
HCID 19689469
N-[6-{2-(4-acetylphenoxy)ethoxy}-5-(4-methylphenyl)pyrimidin-4-yl]-4-tert-butylbenzenesulfonamide
HCID 196895284-tert-butyl-N-[6-{2-(4-ethoxycarbonylphenoxy)ethoxy}-5-(4-methylphenyl)pyrimidin-4-yl]benzenesulfonamide

Reagents, catalysts & solvents 2

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of N-[6-{2-(4-bromophenoxy)ethoxy}-5-(4-methylphenyl)pyrimidin-4-yl]-4-tert-butylbenzenesulfonamide (600 mg), (1-ethoxyvinyl)tributyltin (680 mg), bis(triphenylphosphine)palladium (II) chloride (35.5 mg) and dioxane (24 ml) is refluxed for 18 hours. The mixture is diluted with ethyl acetate, and thereto is added 10% aqueous potassium fluoride solution, and the precipitated crystals are removed by filtration. The filtrate is extracted with ethyl acetate, and the ethyl acetate layer is washed, dried, and concentrated to dryness under reduced pressure. The residue is purified by silica gel column chromatography (solvent; n-hexane/ethyl acetate=5:1~3:1~1:1), and the obtained compounds are each recrystallized from ethyl acetate/diisopropyl ether to give 4-tert-butyl-N-{5-(4-methylphenyl)-6-(2-phenoxyethoxy)pyrimidin-4-yl}benzenesulfonamide (Compound A) (42 mg), N-[6-{2-(4-acetylphenoxy)ethoxy}-5-(4-methylphenyl)pyrimidin-4-yl]-4-tert-butylbenzenesulfonamide (Compound B) (242 mg) and 4-tert-butyl-N-[6-{2-(4-ethoxycarbonylphenoxy)ethoxy}-5-(4-methylphenyl)pyrimidin-4-yl]benzenesulfonamide (Compound C) (58 mg), respectively.

Workup

  1. temperatureis refluxed for 18 hours
  2. customthe precipitated crystals are removed by filtration
  3. extractionThe filtrate is extracted with ethyl acetate
  4. washthe ethyl acetate layer is washed
  5. customdried
  6. concentrationconcentrated to dryness under reduced pressure
  7. customThe residue is purified by silica gel column chromatography (solvent; n-hexane/ethyl acetate=5:1~3:1~1:1)
  8. customeach recrystallized from ethyl acetate/diisopropyl ether

Sources & evidence

ORD record
ord-46a2349036204912b3e748e1dead945d
Source dataset
uspto-grants-1998_03
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US05728706

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes