Butanethiol → (2S,4S)-1-benzyl 2-methyl 4-(biphenyl-4-yl)-4-(butylthio)pyrrolidine-1,2-dicarboxylate

HRID 2425781Notes

Reaction equation

HRID 2425781 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:37])[CH2:34][CH2:35][CH3:36]>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>[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([S:37][CH2:33][CH2:34][CH2:35][CH3:36])[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

Participants

5

Reactant 2

HCID 8012ButanethiolHCID 59386561HCID 59386561, compound

Product 1

HCID 57988328(2S,4S)-1-benzyl 2-methyl 4-(biphenyl-4-yl)-4-(butylthio)pyrrolidine-1,2-dicarboxylateYield 43.3%

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 (2.59 g, 6 mmol) and 1-butanethiol (0.773 mL, 7.20 mmol) in acetonitrile (30 mL) was added Scandium(III) trifluoromethanesulfonate (0.295 g, 0.600 mmol) as solid by one portion at room temperature. The formed pink solution was stirred at this temperature for 26 h. TLC analysis showed starting material was completely consumed. Quenched with sat. ammonium chloride, extracted with EtOAc. Washed the organic with brine, dried over MgSO4, filtered, evaporated in vacuo. The residue was purified by BIOTAGE® column, eluted with gradient 5˜40% EtOAc-hexane to afford the mixture of diastereomers 2.54 g (84%). This oily mixture was purified by BIOTAGE® again, eluted with gradient 0˜20% EtOAc-toluene. The first peak collected from the column afforded by-product (2S,4S)-1-benzyl 2-methyl 4-(biphenyl-4-yl)-4-(butylthio)pyrrolidine-1,2-dicarboxylate (1.54 g, 2.60 mmol, 43.3% yield) as a wax. 1H NMR (500 MHz, CHLOROFORM-d) ppm 0.77 (t, J=7.17, 3H), 1.21-1.24 (m, 2H), 1.28-1.34 (m, 2H), 2.20-2.29 (m, 2H), 2.41-2.46 (m, 1H), 2.86 (dd, J=12.82, 7.32 Hz, 1H), 3.53, 3.75 (s, rotomer, 3H), 3.89 (dd, J=17.09, 11.29 Hz, 1H), 4.23-4.36 (m, 1H), 4.69-4.77 (m, 1H) 5.22-5.30 (m, 2H) 7.28-7.44 (m, 10H), 7.53-7.60 (m, 4H). LC-MS (retention time: 3.28 min, method B), MS m/z 504 (M+H).

Workup

  1. customwas completely consumed
  2. customQuenched with sat. ammonium chloride
  3. extractionextracted with EtOAc
  4. washWashed the organic with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customThe residue was purified by BIOTAGE® column
  9. washeluted with gradient 5˜40% EtOAc-hexane
  10. customto afford
  11. additionthe mixture of diastereomers 2.54 g (84%)
  12. customThis oily mixture was purified by BIOTAGE® again
  13. washeluted with gradient 0˜20% EtOAc-toluene
  14. customThe first peak collected from the column

Sources & evidence

ORD record
ord-d6e060916e624c58925f403fe2a90305
Source dataset
uspto-grants-2011_06
Patent number
US07964560B2

Reaction notes

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