1,1'-Carbonyldiimidazole → 5-((4-Chloro-benzyl)-{1-[2-(3,5-dimethyl-phenyl)-acetyl]-2-methyl-azetidine-2-carbonyl}-amino)-3-oxo-pentanoic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

To a solution of CDI (4 eq) in THF was added 3-((4-chloro-benzyl)-{1-[2-(3,5-dimethyl-phenyl)-acetyl]-2-methyl-azetidine-2-carbonyl}-amino)-propionic acid, compound 65 (1 eq.), the mixture was stirred for 4 h at 20° C., then MgCl2 (4 eq.) and ethyl potassium malonate (5 eq.) were added. The reaction was stirred for 15 h at 20° C. The crude was concentrated under reduced pressure then partitioned between water and EtOAc. The layers were separated and the organic layer was dried over MgSO4, filtered and concentrated under reduced pressure. The crude was purified by chromatography on silica gel (elution with Hept/EtOAc/DCM/MeOH: 50/50/95/5 then 50/50/90/10) to afford 5-((4-chloro-benzyl)-{1-[2-(3,5-dimethyl-phenyl)-acetyl]-2-methyl-azetidine-2-carbonyl}-amino)-3-oxo-pentanoic acid ethyl ester.

Provenance & Evidence