Iodoethane → Methyl (3S*,4R*)-4-(2,4-difluorophenyl)-1-ethylpyrrolidine-3-carboxylate

To a stirred solution of methyl (3S,4R)-4-(2,4-difluorophenyl)pyrrolidine-3-carboxylate, from preparation 19 (10.5 g, 43 mmol) in tetrahydrofuran (215 mL) at room temperature under dry nitrogen was added iodoethane (3.8 mL, 48 mmol) and N,N-diisopropylethylamine (8.3 mL, 48 mmol) in single portions. The resulting mixture was stirred at room temperature under dry nitrogen for 72 hours, then quenched by the addition of water (200 mL) and extracted with ethyl acetate (2×250 mL). The combined organic layers were dried (magnesium sulfate), filtered, and concentrated in vacuo. The residue was purified by flash column chromatography eluting with a 2:1 pentane:ethyl acetate mixture increasing polarity to 1:1. This afforded the title compound as a clear oil (7.9 g, 68%).