Carbon Dioxide → HCID 86673650, compound

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Reaction Steps

To a solution of diisopropyl amine (2.4 g, 24.0 mmol) in 20 mL of anhydrous tetrahydrofuran is added n-butyllithium (8.8 mL, 22.0 mmol, 2.5 M in hexane) dropwise under N2 at −10˜15° C., stir at this temperature for 1 h, add a solution of (S)-2-Biphenyl-4-ylmethyl-5-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester (3a, R1=t-butoxycarbonyl) (7.0 g, 20.0 mmol) in 10 mL of anhydrous tetrahydrofuran dropwise, stir for 1 h, introduce CO2 for 1 h, quench with saturated NH4Cl aqueous solution, extract with ethyl acetate, the combined organic phase is washed with brine, dry over anhydrous sodium sulfate, evaporate the solvent under vacuum, the residue is purified by column chromatography to obtain (S)-5-Biphenyl-4-ylmethyl-2-oxo-pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester (4a, R1=t-butoxycarbonyl, R4=hydroxyl) 1HNMR (400 MHz, CDCl3): 1.59 (s, 1H, Boc), 1.85 (m, 1H, 3CHH), 2.36 (m, 1H, 3CHH), 2.48 (m, 1H, 5-CH2), 2.83 (m, 1H, 5-CH2), 3.09 (m, 1H, 2-CH), 4.40 (m, 1H, 4-CH), 6.10 (d, 1H, C═CHH), 7.23˜7.56 (9H, m, aromatic). The ratio of (3S,5S) to (3R,5S) is 36:64 as determined by HPLC.

Provenance & Evidence