p-Chlorothiophenol → HCID 24852275, compound

HRID 1641552Notes

Reaction equation

HRID 1641552 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([CH2:14][CH2:15][C:16]3([NH:24]C(=O)C)[CH2:21][O:20]C(C)(C)[O:18][CH2:17]3)=[CH:10][CH:9]=2)=[C:4]([F:28])[CH:3]=1.[Cl:29][C:30]1[CH:35]=[CH:34][C:33]([SH:36])=[CH:32][CH:31]=1.C(N(C(C)C)CC)(C)C.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C(Cl)(Cl)Cl.[Pd].[Pd].O>[NH2:24][C:16]([CH2:15][CH2:14][C:11]1[CH:12]=[CH:13][C:8]([C:5]2[CH:6]=[CH:7][C:2]([S:36][C:33]3[CH:34]=[CH:35][C:30]([Cl:29])=[CH:31][CH:32]=3)=[CH:3][C:4]=2[F:28])=[CH:9][CH:10]=1)([CH2:21][OH:20])[CH2:17][OH:18]

Participants

8

Reactant 4

HCID 7815p-ChlorothiophenolHCID 81531DiisopropylethylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)2×HCID 46203835HCID 46203835, compound

Product 1

HCID 24852275HCID 24852275, compoundYield 8.8%

Reagents, catalysts & solvents 3

HCID 11029508Palladium, tris[mu-[(1,2-eta:4,5-eta)-(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one]]di-, compd. with trichloromethane (1:1)Catalyst2×HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A solution of N-{5-[2-(4′-bromo-2′-fluorobiphenyl-4-yl)ethyl]-2,2-dimethyl-1,3-dioxan-5-yl}acetamide (225 mg) of Reference Example 10, 4-chlorobenzenethiol (72 mg), diisopropylethylamine (129 mg), tris(dibenzylideneacetone)dipalladium(0) chloroform adduct (12.9 mg) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos) (14.9 mg) in 1,4-dioxane (2 mL) was heated under reflux for 7 hr under a nitrogen atmosphere. Tris(dibenzylideneacetone)dipalladium(0) chloroform adduct (12.9 mg) and Xantphos (14.9 mg) were added to the reaction mixture, and the mixture was further heated under reflux for 9 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was dissolved in ethanol (4 mL). Concentrated hydrochloric acid (2 mL) was added, and the mixture was stirred at 80° C. for 4 hr. The reaction mixture was concentrated, aqueous potassium carbonate solution was added to the residue, and the precipitated crystals were collected by filtration. The crude crystals were purified by preparative HPLC to give the title compound (19 mg) as white crystals.

Workup

  1. temperatureunder reflux for 7 hr under a nitrogen atmosphere
  2. temperaturethe mixture was further heated
  3. temperatureunder reflux for 9 hr
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe extract was washed with saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. customThe solvent was evaporated under reduced pressure
  8. dissolutionthe obtained residue was dissolved in ethanol (4 mL)
  9. additionConcentrated hydrochloric acid (2 mL) was added
  10. concentrationThe reaction mixture was concentrated
  11. additionaqueous potassium carbonate solution was added to the residue
  12. filtrationthe precipitated crystals were collected by filtration
  13. customThe crude crystals were purified by preparative HPLC

Sources & evidence

ORD record
ord-921811abba9a447886b2e1c7bdc50921
Source dataset
uspto-grants-2012_02
Patent number
US08114902B2

Reaction notes

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