Chlorotrimethylsilane → (2S)-di-tert-butyl 4-(2-ethoxy-2-oxoethyl)-4-hydroxypyrrolidine-1,2-dicarboxylate

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Reaction Steps

Zinc dust (1.05 g, 16 mmol, 1.6 eq.) in a flask was heated with a heat gun two times. Dry THF (10 mL) and chlorotrimethylsilane (0.405 mL, 3.2 mmol, 0.32 eq.) were added to this flask. The suspension was stirred for 15 min at room temp., heated to reflux, and then removed from the heat. (S)-di-tert-butyl 4-oxopyrrolidine-1,2-dicarboxylate (2.85 g, 10 mmol, 1 eq.) and ethyl 2-bromoacetate (1.77 mL, 16 mmol, 1.6 eq.) were combined with dry THF (10 mL), and added slowly to the Zinc suspension at a rate that at which a gentle reflux was observed. The reaction was refluxed for 2 hrs and monitored by TLC. Upon completion, the reaction was concentrated. Chromatography using hexanes and ethyl acetate gave 2.64 g (7.3 mmol) of (2S)-di-tert-butyl 4-(2-ethoxy-2-oxoethyl)-4-hydroxypyrrolidine-1,2-dicarboxylate (A1) as a 4:1 (2S,4S:2S,4R) mixture of the diastereomers. 1H NMR (300 MHz, DMSO) 4.97 (m, 1H), 4.14-4.01 (m, 3H), 3.48-3.33 (m, 2H), 2.56 (m, 2H), 2.35-2.19 (m, 1H), 2.03 (dd, 1H), 1.40-1.35 (m, 18H), 1.18 (t, 3H).

Provenance & Evidence