Malonate Ion → 2-{2-Chloro-4-[2-(2-cyclopentyl-4,6-dioxo-tetrahydro-pyran-2-yl)-ethyl]-phenyl}-2-methyl-propionitrile

Participants

Reaction Conditions

Reaction Steps

5-[3-Chloro-4-(cyano-dimethyl-methyl)-phenyl]-3-cyclopentyl-3-hydroxy-pent-4-enoic acid, from step 1 above, was dissolved in methyl tert-butyl ethylmalonate (3 mL). 4-DMAP (0.16 g, 0.13 mmol) and CDI (0.27 g, 1.68 mmol) were added and the reaction mixture was stirred under argon for 2 hours. In a separate flask was placed magnesium-bis-monoethyl malonate (0.74 g, 2.58 mmol) was suspended in THF (3 mL) and the mixture was heated to 42° C. The acylimidazole solution was added via cannula to the malonate mixture and the reaction was heated to 42° C. for 2 hours. The solvent was removed in vacuo to give a residue that was partitioned between 1 N HCl and EtOAc. The organic layer was dried over MgSO4 and concentrated to a clear oil (0.56 g, 100%).

Provenance & Evidence