m-Fluorobenzenethiol → HCID 24852272, compound

HRID 1641549Notes

Reaction equation

HRID 1641549 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.[F:29][C:30]1[CH:31]=[C:32]([SH:36])[CH:33]=[CH:34][CH:35]=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:10]=[CH:9][C:8]([C:5]2[CH:6]=[CH:7][C:2]([S:36][C:32]3[CH:33]=[CH:34][CH:35]=[C:30]([F:29])[CH:31]=3)=[CH:3][C:4]=2[F:28])=[CH:13][CH:12]=1)([CH2:21][OH:20])[CH2:17][OH:18]

Participants

8

Reactant 4

HCID 75710m-FluorobenzenethiolHCID 81531DiisopropylethylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 46203835HCID 46203835, compound

Product 1

HCID 24852272HCID 24852272, compoundYield 22.7%

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)CatalystHCID 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, 3-fluorobenzenethiol (64 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 6 hr under a nitrogen atmosphere. 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 (47 mg) as white crystals.

Workup

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

Sources & evidence

ORD record
ord-c485d3807e5f4975acc1950d963b4fdc
Source dataset
uspto-grants-2012_02
Patent number
US08114902B2

Reaction notes

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