Triethylamine → Boc-prolylproline methyl ester

Participants

Reaction Steps

METHOD 1 N-tert-butoxycarbonyl L-proline (99.69 g, 0.4631 mol) was dissolved in CH2Cl2 (800 mL). The solution was cooled to 0° C. (icebath) and triethylamine (51.50 g, 0.5089 mol) added. Pivaloyl chloride (61.45 g, 0.5096 mol) was added dropwise, resulting in the precipitation of a white solid. The reaction mixture was stirred for 1 hour at 0° C. before triethylamine (102.99 g, 1.018 mol) was added. Next, L-proline methyl ester hydrochloride (76.87 g, 0.4641 mol) was added in small portions. The icebath was removed and the reaction mixture stirred at room temperature for 17 hours. The volume was increased by addition of CH2Cl2 (2 L) and the solution washed with 30% (w/w) aqueous citric acid (3×1400 mL), saturated NaHCO3 solution (3×1400 mL) and saturated brine (2×1400 mL). The solution was dried with anhydrous MgSO4 and the solvent evaporated affording the title compound as a clear oil (129.14 g, 85%) with spectral characteristics in accordance with literature data.1

Provenance & Evidence