methyl (2R,3S)-2-phenylpyrrolidine-3-carboxylate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To the imine 9A (0.31 g, 1.51 mmol) and triethylamine (0.42 mL, 3.02 mmol) in dichloromethane (15 mL) at 0° C. was added titanium chloride (1.51 mL, 1.0 M in dichloromethane) dropwise under argon. The reaction was stirred at rt for 3 h and then quenched with saturated potassium carbonate. The mixture was filtered through celite and the aqueous layer was extracted with dichloromethane (2×). The organic extracts were combined, washed with brine and dried over sodium sulfate. The solvent was evaporated and the crude residue was purified by preparative HPLC equipped with a YMC ODS S5 (30×100 mm) column. The separation was performed using a linear gradient (solvent A: 10% acetonitrile-90% water-0.1% TFA; solvent B: 90% acetonitrile-90% water-0.1% TFA; 0 to 100% B in 12 min with a flow rate of 40 mL/min to give 0.095 g of 9B as a solid. 1H NMR (400 MHz, Methanol-d4) δ ppm 2.50 (m, 2H) 3.42 (s, 3H) 3.55 (m, 1H) 3.72 (m, 2H) 4.98 (d, J=7.09 Hz, 1H) 7.36 (m, 2H) 7.44 (m, 3H). quenched with saturated potassium carbonate The mixture was filtered through celite the aqueous layer was extracted with dichloromethane (2×) washed with brine dried over sodium sulfate The solvent was evaporated the crude residue was purified by preparative HPLC equipped with a YMC ODS The separation