4-Methoxybenzenethiol → 3-[4-(4-Methoxy-phenylsulfanyl)-2-methyl-phenyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 503929Notes

Reaction equation

HRID 503929 reaction equation
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.[CH3:43][O:44][C:45]1[CH:50]=[CH:49][C:48]([SH:51])=[CH:47][CH:46]=1.CCN(C(C)C)C(C)C.[C:61]([O:65][C:66]([N:68]1[CH2:72][CH2:71][CH:70]([C:73]2[CH:78]=[CH:77][C:76](Br)=[CH:75][C:74]=2[CH3:80])[CH2:69]1)=[O:67])([CH3:64])([CH3:63])[CH3:62].OS([O-])(=O)=O.[K+].[O-]S([O-])(=O)=O.[Na+].[Na+]>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.[Pd].[Pd]>[C:61]([O:65][C:66]([N:68]1[CH2:72][CH2:71][CH:70]([C:73]2[CH:78]=[CH:77][C:76]([S:51][C:48]3[CH:49]=[CH:50][C:45]([O:44][CH3:43])=[CH:46][CH:47]=3)=[CH:75][C:74]=2[CH3:80])[CH2:69]1)=[O:67])([CH3:64])([CH3:63])[CH3:62]

Participants

8

Reactant 5

HCID 127654-MethoxybenzenethiolHCID 81531DiisopropylethylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 66877329Tert-butyl 3-(4-bromo-2-methylphenyl)pyrrolidine-1-carboxylateHCID 86586342KHSO4 Na2SO4

Product 1

HCID 668774633-[4-(4-Methoxy-phenylsulfanyl)-2-methyl-phenyl]-pyrrolidine-1-carboxylic acid tert-butyl esterYield 77.5%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

Tris(dibenzylideneacetone)dipalladium(0) (336 mg, 0.3674 mmol), 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene (425 mg, 0.7347 mmol), 4-methoxy-benzenethiol (361 μL, 2.939 mmol) and DIPEA (0.538 mL, 5.878 mmol) were added to a solution of 3-(4-bromo-2-methyl-phenyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (1.0 g, 2.939 mmol) in 1,4-dioxane (10 mL). The reaction mixture was heated at reflux for 18 hours, then cooled to room temperature, and a solution of 10% KHSO4/Na2SO4 was added. The mixture was extracted with EtOAc, and the combined organic extracts were washed with water and brine, dried over Na2SO4, filtered and evaporated under reduced pressure. The resulting crude material was purified via flash chromatography (hexane/EtOAc, 95/5) to give 0.91 g (77% yield) of 3-[4-(4-methoxy-phenylsulfanyl)-2-methyl-phenyl]-pyrrolidine-1-carboxylic acid tert-butyl ester as a white foam.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 18 hours
  3. extractionThe mixture was extracted with EtOAc
  4. washthe combined organic extracts were washed with water and brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customevaporated under reduced pressure
  8. customThe resulting crude material was purified via flash chromatography (hexane/EtOAc, 95/5)

Sources & evidence

ORD record
ord-cae1fada38094df483792a381223b405
Source dataset
uspto-grants-2010_08
Patent number
US07776910B2

Reaction notes

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