(S)-2-benzyl 1-tert-butyl 4-oxopyrrolidine-1,2-dicarboxylate → (S)-2-benzyl 1-tert-butyl 4-ethylidenepyrrolidine-1,2-dicarboxylate

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Reaction Steps

(2S,4S)-1-(tert-butoxycarbonyl)-4-ethylpyrrolidine-2-carboxylic acid: To a mixture of KOtBu (0.176 g, 1.57 mmol) and (ethyl)triphenylphosphonium bromide (0.581 g, 1.57 mmol) was added THF (3.1 mL) at rt. The mixture was stirred for 1 h. Next, a solution of (S)-2-benzyl 1-tert-butyl 4-oxopyrrolidine-1,2-dicarboxylate (0.200 g, 0.581 mmol) dissolved in THF (1 mL) was added via cannula and the flask was rinsed with THF (0.5 mL). The reaction was stirred overnight at rt. The reaction was quenched with water and diluted with EtOAc. The layers were separated and the organic layer was washed with brine, dried (MgSO4), and concentrated. The crude product was purified by silica gel chromatography to provide (S)-2-benzyl 1-tert-butyl 4-ethylidenepyrrolidine-1,2-dicarboxylate as a colorless oil as a mixture of E/Z isomers. The E/Z mixture was used directly in the next reaction. (S)-2-benzyl 1-tert-butyl 4-ethylidenepyrrolidine-1,2-dicarboxylate (0.0866 g, 0.261 mmol) was dissolved in EtOH (5.2 mL) and 10% Pd/C (0.092 g, 0.086 mmol) was added. The reaction was purged with argon and then H2 and stirred overnight under a H2 balloon. The reaction was filtered and concentrated. The crude product was purified by silica gel chromatography to provide 57A (colorless oil, 0.0358 g, 0.147 mmol, 23.5% yield). LC-MS Anal. Calc'd for C12H21NO4 243.30. found [M+H] 244.0. 1H NMR (400 MHz, chloroform-d) δ ppm 4.13-4.34 (1 H, m), 3.63-3.83 (1 H, m), 2.91-3.04 (1 H, m), 2.31-2.51 (1 H, m), 1.99-2.12 (1 H, m, J=14.31, 10.18, 7.15, 7.15 Hz), 1.54-1.82 (1 H, m), 1.33-1.51 (11 H, m), 0.91 (3 H, t, J=7.02 Hz).

Provenance & Evidence