Dichloromethane → Ethyl (S)-1-Cbz-4-oxopyrrolidine-2-carboxylate

Participants

Reaction Steps

To a round bottom flask containing 14.0 g (52.8 mmol) of N-Cbz-4-hydroxy-L-proline 8 was added 26 mL acetone. The solution was cooled on ice bath where 8.12 mL (0.106 mmol; 2 eq) of Jones reagent (CrO3, H2SO4, 1.3 M in water) was added. The mixture was allowed to warm to room temperature and stir for 3 h where the reaction appeared to be complete, as determined by TLC. The reaction was quenched by the addition of 6 mL isopropanol. After stirring for another 2 h the flask was placed on a glass socket rotovap and the isopropanol/acetone was removed by reduced pressure. The remaining green residue was then diluted into 200 mL water, salted with NaCl and extracted with EtOAc (3×200 mL). The organic extracts were combined, dried with MgSO4, filtered and concentrated to an oil. The remaining yellow oil was then separated by silica gel (90% CH2Cl2, 9% MeOH, 1% AcOH, Rf=0.3). The fractions containing the product were combined and concentrated by rotovap to a solid residue and then recrystallized from CH2Cl2 leaving 9.86 g (37.5 mmol) of N-Cbz-4-keto-L-proline, a 71% yield. The product material was used in the next synthetic step without further purification.

Provenance & Evidence