Allyl Mercaptan → (2S,4R)-1-benzyl 2-methyl 4-(allylthio)-4-(biphenyl-4-yl)pyrrolidine-1,2-dicarboxylate

HRID 2061416Notes

Reaction equation

HRID 2061416 reaction equation
[C:1]1([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:6]=[CH:5][C:4]([C@@:7]2(O)[CH2:11][N:10]([C:12]([O:14][CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[O:13])[C@H:9]([C:22]([O:24][CH3:25])=[O:23])[CH2:8]2)=[CH:3][CH:2]=1.[CH2:33]([SH:36])[CH:34]=[CH2:35]>C(#N)C.FC(F)(F)S([O-])(=O)=O.[Sc+3].FC(F)(F)S([O-])(=O)=O.FC(F)(F)S([O-])(=O)=O>[CH2:33]([S:36][C@:7]1([C:4]2[CH:5]=[CH:6][C:1]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[CH:2][CH:3]=2)[CH2:11][N:10]([C:12]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[O:13])[C@H:9]([C:22]([O:24][CH3:25])=[O:23])[CH2:8]1)[CH:34]=[CH2:35]

Participants

5

Reactant 2

HCID 13367Allyl MercaptanHCID 59386561HCID 59386561, compound

Product 1

HCID 57988337(2S,4R)-1-benzyl 2-methyl 4-(allylthio)-4-(biphenyl-4-yl)pyrrolidine-1,2-dicarboxylateYield 22.15%

Reagents, catalysts & solvents 2

HCID 2734571Scandium(III) triflateCatalystHCID 6342AcetonitrileSolvent

Procedure

To a clear solution of (2S,4R)-1-benzyl 2-methyl 4-(biphenyl-4-yl)-4-hydroxypyrrolidine-1,2-dicarboxylate (3236 mg, 7.5 mmol) and prop-2-ene-1-thiol (834 mg, 9.00 mmol) in Acetonitrile (40 mL) was added Scandium(III) trifluoromethanesulfonate (369 mg, 0.750 mmol) as solid by one portion at room temperature. The formed pink solution was stirred at this temperature for 20 h. Quenched with sat. ammonium chloride, extracted with EtOAc. Washed the organic with brine, dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by Biotage column, eluted with 5%˜50% EtOAc-Hexane to afford a mixture of the diasteromers (2.88 g, 79%) and the starting material (0.600 g, 18%). This mixture of the diasteromers was purified by Biotage column again, eluted with 2%˜8% EtOAc-Toluene to afford the desired product (2S,4R)-1-benzyl 2-methyl 4-(allylthio)-4-(biphenyl-4-yl)pyrrolidine-1,2-dicarboxylate (900 mg, 1.661 mmol, 22.15% yield) as the second peak collected from the column as a viscous oil. 1H NMR (500 MHz, CHLOROFORM-D) δ ppm 2.59-2.76 (m, 1 H) 2.78-2.93 (m, 3 H) 3.60 (s, 1.5 H) 3.77 (s, 1.5 H) 3.92 (d, J=11.60 Hz, 1 H) 4.17-4.31 (m, 1 H) 4.34-4.49 (m, 1 H) 4.92-5.07 (m, 2 H) 5.08-5.34 (m, 2 H) 5.53-5.72 (m, 1 H) 7.23-7.41 (m, 6 H) 7.45 (t, J=7.63 Hz, 3 H) 7.48-7.67 (m, 5 H).

Workup

  1. customQuenched with sat. ammonium chloride
  2. extractionextracted with EtOAc
  3. washWashed the organic with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by Biotage column
  8. washeluted with 5%˜50% EtOAc-Hexane
  9. customto afford
  10. additiona mixture of the diasteromers (2.88 g, 79%)
  11. additionThis mixture of the diasteromers
  12. customwas purified by Biotage column again
  13. washeluted with 2%˜8% EtOAc-Toluene

Sources & evidence

ORD record
ord-3fc4dd328f144a4f8a776346ab3efa09
Source dataset
uspto-grants-2012_10
Patent number
US08283310B2

Reaction notes

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