2-Bromobenzonitrile → 3-[4-(2-Cyano-phenylsulfanyl)-2-methoxy-phenyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 503934Notes

Reaction equation

HRID 503934 reaction equation
Br[C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[C:4]#[N:5].CCN(C(C)C)C(C)C.[C:19]([O:23][C:24]([N:26]1[CH2:30][CH2:29][CH:28]([C:31]2[CH:36]=[CH:35][C:34]([SH:37])=[CH:33][C:32]=2[O:38][CH3:39])[CH2:27]1)=[O:25])([CH3:22])([CH3:21])[CH3:20].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].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>[C:19]([O:23][C:24]([N:26]1[CH2:30][CH2:29][CH:28]([C:31]2[CH:36]=[CH:35][C:34]([S:37][C:2]3[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=3[C:4]#[N:5])=[CH:33][C:32]=2[O:38][CH3:39])[CH2:27]1)=[O:25])([CH3:22])([CH3:21])[CH3:20]

Participants

8

Reactant 4

HCID 162722-BromobenzonitrileHCID 81531DiisopropylethylamineHCID 594283563-(4-Mercapto-2-methoxy-phenyl)-pyrrolidine-1-carboxylic acid tert-butyl esterHCID 86586342KHSO4 Na2SO4

Product 1

HCID 594284293-[4-(2-Cyano-phenylsulfanyl)-2-methoxy-phenyl]-pyrrolidine-1-carboxylic acid tert-butyl esterYield 90%

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

Pd2(dba)3 (13 mg, 0.01414 mmol), Xantphos (16 mg, 0.02828 mmol), 2-bromobenzonitrile (0.103 mg, 0.5655 mmol) and DIPEA (0.103 mL, 1.131 mmol) were added to a solution of 3-(4-mercapto-2-methoxy-phenyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.175 g, 0.5655 mmol) in 1,4-dioxane (10 mL). The reaction mixture was heated at reflux for 16 hours, then cooled 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, 7/3) to give 0.209 g (90% yield) of 3-[4-(2-cyano-phenylsulfanyl)-2-methoxy-phenyl]-pyrrolidine-1-carboxylic acid tert-butyl ester as a clear oil.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 16 hours
  3. temperaturecooled
  4. extractionThe 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 resulting crude material was purified via flash chromatography (hexane/EtOAc, 7/3)

Sources & evidence

ORD record
ord-f8f3f83919bf4a86ae1402469fa4f37c
Source dataset
uspto-grants-2010_08
Patent number
US07776910B2

Reaction notes

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