2-Propanethiol → (2S,4S)-1-benzyl 2-methyl 4-(biphenyl-4-yl)-4-(isopropylthio)pyrrolidine-1,2-dicarboxylate

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Reaction Steps

To a clear solution of (2S,4R)-1-benzyl 2-methyl 4-(biphenyl-4-yl)-4-hydroxypyrrolidine-1,2-dicarboxylate (1.82 g, 4.22 mmol) and 2-propanethiol (0.470 mL, 5.06 mmol) in acetonitrile (20 mL) was added Scandium(III) trifluoromethanesulfonate (0.208 g, 0.422 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 1.44 g (70%). This oily mixture was purified by BIOTAGE® again, eluted with gradient 0˜20% EtOAc-toluene to yield the by-product (2S,4S)-1-benzyl 2-methyl 4-(biphenyl-4-yl)-4-(isopropylthio)pyrrolidine-1,2-dicarboxylate (1.05 g, 1.930 mmol, 45.8% yield) as a white foam and the desired product (2S,4R)-1-benzyl 2-methyl 4-(biphenyl-4-yl)-4-(isopropylthio)pyrrolidine-1,2-dicarboxylate (450 mg, 0.827 mmol, 19.61% yield) as a white foam. 1H NMR (500 MHz, MeOD) ppm 0.96 (d, J=6.71 Hz, 1.5H, rotamer), 1.00 (d, J=6.71 Hz, 1.5H, rotamer), 1.07 (d, J=7.02 Hz, 3H), 2.48-2.57 (m, 1H), 2.57-2.68 (m, 1H), 2.97-3.07 (m, 1H), 3.65 (s, 1.5H, rotamer), 3.77 (s, 1.5H, rotamer), 3.82-3.91 (m, 1H), 4.26-4.42 (m, 2H), 5.00-5.28 (m, 2H), 7.25-7.72 (m, 14H). LC-MS (retention time: 3.39 min, method B), MS m/z 490 (M+H).

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