Hydrochloric Acid → HCID 86684764, compound

Participants

Reaction Conditions

Reaction Steps

MgCl2 (153 g, 1640 mmol) was added in one portion to a solution of ethyl potassium malonate (354.9 g, 2085 mmol) in THF (2500 mL). The reaction mixture was stirred for 7 h at 65-70° C. and then at 30° C. overnight. A solution of Cbz-L-Proline (400 g) in THF (1000 mL) was slowly added to a mixture of CDI (312.1 g, 1924.8 mmol) in THF (1500 mL) and stirred at 30° C. for 2 h. The solution was added to the ethyl malonate mixture over 20 min at 20-30° C. and stirred overnight at 30° C. The mixture was cooled to 20° C. and neutralized with diluted HCl (4 N, 1800 mL). The solution was concentrated and the product was dissolved in ethyl acetate and rinsed with 5% aqueous sodium bicarbonate. The organic layer was concentrated and the residue was purified by flash column chromatography (eluent: petroleum ether:ethyl acetate=20:1 to 3:1) to give pure (S)-benzyl 2-(3-ethoxy-3-oxopropanoyl)pyrrolidine-1-carboxylate (460 g, 90% yield). Method A4 Rt: 1.23 min. m/z: 341.9 (M+Na)+ Exact mass: 319.1

Provenance & Evidence