N-Boc-4-hydroxy-D-proline, trans- → (2S)-1-(tert-butoxycarbonyl)-4-oxopyrrolidine-2-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of (2R,4S)-1-(tert-butoxycarbonyl)-4-hydroxypyrrolidine-2-carboxylic acid (92 g, 0.398 mol) in isopropyl acetate (460 mL) was added TEMPO (2.49 g, 0.05 eq) at 0° C. A solution of NaClO (12.5 wt %, 370 mL) was added dropwise to the reaction mixture while maintaining the temperature at 0-5° C. The reaction was slowly allowed to warm to room temperature and stirred at room temperature overnight. The organic layer was separated and the aqueous layer was treated with 1M KHSO4 solution and extracted with isopropyl acetate (2×150 mL). The combined organic layers were washed with 5% Na2S2O3 (100 mL), brine, dried (Na2SO4), filtered and evaporated to provide the title compound as a solid. It was triturated with acetonitrile (40 mL), filtered and dried to give a white solid (52.3 g). The filtrate was concentrated, treated with 50% ethyl acetate in hexanes (20 mL) and stored in refrigerator for overnight before being filtered and dried to give a white solid (3.94 g). Totally obtained 56.24 g (62%). 1H NMR (500 MHz, DMSO-d6): 12.99 (br s, 1H), 4.54-4.50 (m, 1H), 3.84-3.77 (m, 1H), 3.68-3.63 (m, 1H), 3.15-3.06 (m, 1H), ˜2.49 (m, 1H, overlapped with DMSO), 1.40 and 1.37 (2 s, 9H).

Provenance & Evidence