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

HRID 503925Notes

Reaction equation

HRID 503925 reaction equation
[CH3:1][Si:2]([CH3:7])([CH3:6])[CH2:3][CH2:4][SH:5].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.CCN(C(C)C)C(C)C.[C:59]([O:63][C:64]([N:66]1[CH2:70][CH2:69][C@@H:68]([C:71]2[CH:76]=[CH:75][C:74](Br)=[CH:73][CH:72]=2)[CH2:67]1)=[O:65])([CH3:62])([CH3:61])[CH3:60].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:59]([O:63][C:64]([N:66]1[CH2:70][CH2:69][C@@H:68]([C:71]2[CH:76]=[CH:75][C:74]([S:5][CH2:4][CH2:3][Si:2]([CH3:7])([CH3:6])[CH3:1])=[CH:73][CH:72]=2)[CH2:67]1)=[O:65])([CH3:62])([CH3:60])[CH3:61]

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 2055212-(Trimethylsilyl)ethanethiolHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 59428435(S)-3-(4-bromo-phenyl)-pyrrolidine-1-carboxylic acid tert-butyl esterHCID 86586342KHSO4 Na2SO4

Product 1

HCID 59428461(S)-3-[4-(2-trimethylsilanyl-ethylsulfanyl)-phenyl]-pyrrolidine-1-carboxylic acid tert-butyl esterYield 100.3%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
97.5 °C

Procedure

2-(Trimethylsilyl)ethane thiol (0.33 mL, 2.1 mmol), Pd2(dba)3 (183.9 mg), Xantphos (231.4 mg) and DIPEA (0.296 mL) were added to a solution of (S)-3-(4-bromo-phenyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (528 mg, 1.618 mmol) in 1,4-dioxane (7 mL) under nitrogen atmosphere. The reaction mixture was heated at 95-100° C. for 20 hours. After cooling to room temperature, a solution of 10% KHSO4/Na2SO4 was added and the mixture was extracted with EtOAc. The combined organic extracts were washed with brine, dried over Na2SO4, filtered, and evaporated under reduced pressure. The residue was purified via flash chromatography (hexane/EtOAc, 94/6) to give 616 mg (quantitative yield) of (S)-3-[4-(2-trimethylsilanyl-ethylsulfanyl)-phenyl]-pyrrolidine-1-carboxylic acid tert-butyl ester.

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionthe mixture was extracted with EtOAc
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customevaporated under reduced pressure
  7. customThe residue was purified via flash chromatography (hexane/EtOAc, 94/6)

Sources & evidence

ORD record
ord-bd20e92e6b154111965b251020c83993
Source dataset
uspto-grants-2010_08
Patent number
US07776910B2

Reaction notes

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