Diisopropylethylamine → 3-[2-Methoxy-4-(2-trimethylsilanyl-ethylsulfanyl)-phenyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 503912Notes

Reaction equation

HRID 503912 reaction equation
[CH2:1]([Si:3]([CH2:9]C)([CH2:7]C)[CH2:4][CH2:5][SH:6])C.CCN(C(C)C)C(C)C.[C:20]([O:24][C:25]([N:27]1[CH2:31][CH2:30][CH:29]([C:32]2[CH:37]=[CH:36][C:35](Br)=[CH:34][C:33]=2[O:39][CH3:40])[CH2:28]1)=[O:26])([CH3:23])([CH3:22])[CH3:21].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].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>[C:20]([O:24][C:25]([N:27]1[CH2:31][CH2:30][CH:29]([C:32]2[CH:37]=[CH:36][C:35]([S:6][CH2:5][CH2:4][Si:3]([CH3:1])([CH3:7])[CH3:9])=[CH:34][C:33]=2[O:39][CH3:40])[CH2:28]1)=[O:26])([CH3:23])([CH3:22])[CH3:21]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 205579Ethanethiol, 2-(triethylsilyl)-HCID 668773131-Boc-3-(4-bromo-2-methoxyphenyl)pyrrolidineHCID 86586342KHSO4 Na2SO4

Product 1

HCID 668782423-[2-Methoxy-4-(2-trimethylsilanyl-ethylsulfanyl)-phenyl]-pyrrolidine-1-carboxylic acid tert-butyl esterYield 66.1%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

Tris(dibenzylideneacetone)dipalladium(0) (32 mg, 0.03509 mmol), 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene (40 mg, 0.07017 mmol), 2-(triethylsilyl)ethanethiol (57 μL, 1.403 mmol) and DIPEA (0.257 mL, 2.807 mmol) were added to a solution of 3-(4-bromo-2-methoxy-phenyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.50 g, 1.403 mmol) in 1,4-dioxane (10 mL). The reaction mixture was heated at reflux for 18 hours. The reaction mixture was cooled and a solution of 10% KHSO4/Na2SO4 was added. The resulting 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 residue was purified via flash chromatography (hexane/EtOAc, 95/5) to give 0.380 g (66% yield) of 3-[2-methoxy-4-(2-trimethylsilanyl-ethylsulfanyl)-phenyl]-pyrrolidine-1-carboxylic acid tert-butyl ester as a clear oil.

Workup

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

Sources & evidence

ORD record
ord-dfec158e88aa47178396c8315a09528e
Source dataset
uspto-grants-2010_08
Patent number
US07776910B2

Reaction notes

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