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

Provenance & Evidence