4-Fluorobenzyl bromide → (2S,4R)-1-tert-butyl 2-ethyl 4-(4-fluorobenzyl)-5-oxopyrrolidine-1,2-dicarboxylate

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Reaction Steps

Step (b) 1M LiHMDS (27.5 mL, 27.5 mmol) was added to a solution of (S)-1-tert-butyl 2-ethyl 5-oxopyrrolidine-1,2-dicarboxylate (6.4 g, 25 mmol) in THF (20 mL) at −78° C. The mixture was stirred for 50 minutes and then 4-fluorobenzyl bromide (3.25 mL, 26.5 mmol) in THF (2 mL) was added dropwise. The mixture was stirred for 1 hour and 40 minutes and quenched with excess saturated ammonium chloride. The mixture was warmed to ambient temperature and extracted with ethyl acetate. The extract was washed with water and then brine, dried over magnesium sulfate, filtered and concentrated. The solid residue was dissolved in a 3:1 hexane/methyl tert-butyl ether solvent mixture (100 mL) and slow crystallization was allowed at ambient temperature. The mixture was cooled to 0° C. and the solid was collected by filtration, washed with a 3:1 hexane/methyl tert-butyl ether solvent mixture (50 mL) and dried to give (2S,4R)-1-tert-butyl 2-ethyl 4-(4-fluorobenzyl)-5-oxopyrrolidine-1,2-dicarboxylate (3.59 g, 39%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.15-7.12 (m, 2H), 7.01-6.96 (m, 2H), 4.47 (dd, J=2.0, 9.2, 1H), 4.22-4.17 (m, 2H), 3.22 (dd, J=4.4, 14.4, 1H), 2.94-2.85 (m, 1H), 2.71-2.65 (m, 1H), 2.08-1.94 (m, 2H), 1.50 (s, 9H), 1.26 (t, 3H).

Provenance & Evidence