Thiophenol → (2S,4R)-1-(1-(4-chlorophenyl)cyclopropanecarbonyl)-N-(1-cyanocyclopropyl)-4-(phenylthio)pyrrolidine-2-carboxamide

HRID 1697733Notes

Reaction equation

HRID 1697733 reaction equation
C1(S(O[C@H:11]2[CH2:15][C@@H:14]([C:16](=[O:23])[NH:17][C:18]3([C:21]#[N:22])[CH2:20][CH2:19]3)[N:13]([C:24]([C:26]3([C:29]4[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=4)[CH2:28][CH2:27]3)=[O:25])[CH2:12]2)(=O)=O)C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+].O1CCCC1.[C:47]1([SH:53])[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1>CC(N(C)C)=O.O>[Cl:35][C:32]1[CH:31]=[CH:30][C:29]([C:26]2([C:24]([N:13]3[CH2:12][C@H:11]([S:53][C:47]4[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=4)[CH2:15][C@H:14]3[C:16]([NH:17][C:18]3([C:21]#[N:22])[CH2:20][CH2:19]3)=[O:23])=[O:25])[CH2:28][CH2:27]2)=[CH:34][CH:33]=1

Participants

7

Reactant 4

HCID 7969ThiophenolHCID 8028Tetrahydrofuran2×HCID 11430Potassium CarbonateHCID 86646867(3S,5S)-1-(1-(4-chlorophenyl)cyclopropanecarbonyl)-5-(1-cyanocyclopropylcarbamoyl)pyrrolidin-3-yl Benzenesulfonate

Product 1

HCID 67277395(2S,4R)-1-(1-(4-chlorophenyl)cyclopropanecarbonyl)-N-(1-cyanocyclopropyl)-4-(phenylthio)pyrrolidine-2-carboxamideYield 101.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
22 °C

Procedure

To a suspension of (3S,5S)-1-(1-(4-chlorophenyl)cyclopropanecarbonyl)-5-(1-cyanocyclopropylcarbamoyl)pyrrolidin-3-yl benzenesulfonate (example 457c; 200 mg) and potassium carbonate (134 mg) in dimethylacetamide (1 mL) was added at tetrahydrofuran (1.2 mL) at room temperature THF and benzenethiol (50.7 mg). The reaction mixture was stirred at 22° C. for 20 hr then poured into water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate and filtered. The crude mixture was concentrated to dryness and purified by chromatography on silica gel to yield the title compound as a colorless oil (184 mg; 89%). MS (ESI): m/z=466.13 [M+H]+.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationThe crude mixture was concentrated to dryness
  6. custompurified by chromatography on silica gel

Sources & evidence

ORD record
ord-44de6e0ec5d14a138b9c3166326cfdc1
Source dataset
uspto-grants-2012_04
Patent number
US08163793B2

Reaction notes

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