Water → Methyl (2S,4S)-1-[(3-cyanophenyl)sulfonyl]-4-hydroxypyrrolidine-2-carboxylate

Participants

Reaction Conditions

Reaction Steps

Methyl (4S)-4-hydroxyprolinate (52.0 g, 0.286 mol) was dissolved in 500 mL CH2Cl2 and cooled to 0° C. Triethylamine (83.6 mL, 0.600 mol) was added, followed by 3-cyanobenzenesulfonyl chloride (55.0, 0.273 mol) slowly. The reaction mixture was stirred at room temperature overnight. Water was added, and the aqueous layer was extracted three times with CH2Cl2. The combined organic layers were washed with 1N HCl, H2O, 1N NaOH, and brine, dried over MgSO4, and concentrated to give a viscous residue. Ethyl acetate (300 mL) was added to completely dissolve the residue. Approximately 100 mL hexanes was added slowly until the solution became slightly cloudy. The mixture was then stirred overnight to allow the product to precipitate. The solid was filtered and rinsed two times with 30% EtOAc/hexanes to give the desired product as an off-white powder (66.2 g, 78%). 1H-NMR (CDCl3, 500 MHz) δ 8.20-8.18 (m, 1H), 8.15-8.12 (m, 1H), 7.92-7.89 (m, 1H), 7.72 (t, 1H), 4.51-4.47 (m, 1H), 4.42 (br s, 1H), 3.74 (s, 3H), 3.53-3.49 (m, 1H), 3.46-3.43 (m, 1H), 3.39 (br s, 1H), 2.29-2.25 (m, 1H), 2.21-2.02 (m, 1H). MS (ESI) calculated for C13H14N2O5S 310.3, observed m/e 311.2 (MH+).

Provenance & Evidence