m-Fluorobenzenethiol → HCID 66877378, compound

HRID 503958Notes

Reaction equation

HRID 503958 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][C:16](Br)=[CH:15][C:14]=2[C:20]([O:22][CH2:23][CH3:24])=[O:21])=[CH:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].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.CCN(C(C)C)C(C)C.[F:76][C:77]1[CH:78]=[C:79]([SH:83])[CH:80]=[CH:81][CH:82]=1>O1CCOCC1.[Cl-].[Na+].O.[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][C:16]([S:83][C:79]3[CH:80]=[CH:81][CH:82]=[C:77]([F:76])[CH:78]=3)=[CH:15][C:14]=2[C:20]([O:22][CH2:23][CH3:24])=[O:21])=[CH:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 75710m-FluorobenzenethiolHCID 81531DiisopropylethylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 66876818HCID 66876818, compound

Product 1

HCID 66877378HCID 66877378, compoundYield 53.3%

Reagents, catalysts & solvents 3

HCID 9832798Tris(dibenzylideneacetone) dipalladiumCatalystHCID 312751,4-DioxaneSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
90 °C

Procedure

3-(4-Bromo-2-ethoxycarbonyl-phenyl)-pyrrole-1-carboxylic acid tert-butyl ester (1.65 g, 4.180 mmol) was dissolved in 25 ml of dioxane. Tris(dibenzylideneacetone) dipalladium(0) (478 mg. 0.522 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (605 mg, 1.044 mmol), and DIPEA (1.82 ml, 10.45 mmol) were added followed by 3-fluorothiophenol (0.353 ml, 4.180 mmol). The mixture was heated to 90° C. overnight. The mixture was cooled to 5° C. and diluted with pH 2 buffer. Brine was added and the mixture was extracted with EtOAc. The combined extracts were washed with brine, dried over Na2SO4, filtered through a GF/F filter and concentrated under reduced pressure. The residue was purified by flash chromatography (Hexane/EtOAc 9/1) to give 983 mgs (53.02%) of 3-[2-Ethoxycarbonyl-4-(3-fluoro-phenylsulfanyl)-phenyl]-pyrrole-1-carboxylic acid tert-butyl ester as a clear oil.

Workup

  1. temperatureThe mixture was cooled to 5° C.
  2. additiondiluted with pH 2 buffer
  3. extractionthe mixture was extracted with EtOAc
  4. washThe combined extracts were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered through a GF/F
  7. filtrationfilter
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by flash chromatography (Hexane/EtOAc 9/1)

Sources & evidence

ORD record
ord-a7c7ea2b3eab4149abe44414fdfc09b3
Source dataset
uspto-grants-2010_08
Patent number
US07776910B2

Reaction notes

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