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

HRID 1666529Notes

Reaction equation

HRID 1666529 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 hours. TLC analysis showed starting material was completely consumed. Quenched with saturated ammonium chloride, extracted with ethyl acetate. Washed the organic phase with brine, dried over MgSO4, filtered, concentrated in vacuo. The residue was purified by BIOTAGE® column, eluted with gradient 5˜40% ethyl acetate-hexane to afford the mixture of diastereomers 2.54 g (84%). This oily mixture was purified by BIOTAGE® again, eluted with gradient 0˜20% ethyl acetate-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) δ ppm 0.77 (t, J=7.17, 3H), 1.21-1.24 (m, 2 H), 1.28-1.34 (m, 2 H), 2.20-2.29 (m, 2 H), 2.41-2.46 (m, 1 H), 2.86 (dd, J=12.82, 7.32 Hz, 1 H), 3.53, 3.75 (s, rotomer, 3 H), 3.89 (dd, J=17.09, 11.29 Hz, 1 H), 4.23-4.36 (m, 1 H), 4.69-4.77 (m, 1 H) 5.22-5.30 (m, 2 H) 7.28-7.44 (m, 10 H), 7.53-7.60 (m, 4 H). LC-MS (retention time: 3.28 min, method B), MS m/z 504 (M+H).

Workup

  1. customwas completely consumed
  2. customQuenched with saturated ammonium chloride
  3. extractionextracted with ethyl acetate
  4. washWashed the organic phase with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by BIOTAGE® column
  9. washeluted with gradient 5˜40% ethyl acetate-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% ethyl acetate-toluene
  14. customThe first peak collected from the column

Sources & evidence

ORD record
ord-ac19cf656a35442ab670f3d1624d19b0
Source dataset
uspto-grants-2011_10
Patent number
US08044023B2

Reaction notes

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