p-Toluenesulfonic acid → (2S,4S)-4-Fluoropyrrolidine-2-carbonitrile 4-methylbenzenesulfonate

Participants

Reaction Steps

To a stirred solution of Step 1 intermediate (40 g, 186.72 mmol) in acetonitrile (400 ml) was added p-toluene sulfonic acid (64.3 g, 373.33 mmol) and the solution was stirred at for 24 h at room temperature under nitrogen atmosphere. The solvent was evaporated under reduced pressure to afford a brown residue, which was triturated with petroleum ether (100 ml) to give a filterable solid. The solid was collected by filtration and dried to give 45 g of the product as an off-white solid; 1H NMR (CDCl3, 300 MHz) δ 2.31 (s, 3H), 2.37-2.65 (m, 2H), 3.76-3.87 (m, 2H), 5.10 (br s, 2H), 5.33 (br d, J=51.6 Hz, 1H), 7.19 (d, J=8.1 Hz, 2H), 7.75 (d, J=8.1 Hz, 2H).

Provenance & Evidence