HCID 59468929, compound → HCID 59468973, compound

Participants

Reaction Steps

To a solution of 1-(1,1-dimethylethyl) 2-methyl (2R,5R)-2-(cyanomethyl)-5-{4-[(phenylmethyl)oxy]phenyl}-1,2-pyrrolidinedicarboxylate (D24, 2.7 g, 5.99 mmol): in methanol (50 ml) was added Raney Nickel (slurry in water) and the mixture was stirred under a hydrogen atmosphere (7 atmospheres) for 14 hours. The catalyst was filtered off, the solvent removed under reduced pressure, and the solid residue was treated with toluene (3×20 ml) and dried under vacuum. The dry white solid obtained was refluxed in methanol (40 ml) for five hours until cyclization was complete. The solvent was removed under reduced pressure and the crude material purified by chromatography on silica gel using dichloromethane/methanol (95:5 to 90:10) to afford the title compound as a white solid (1.35 g, 68%); Rt (HPLC): 3.91 min; R (dichloromethane:methanol=9:1): 0.41; MS: (ES/+) m/z: 665 [2M+Na+], 355 [M+Na+]; C18H24N2O4 requires 332; 1H NMR (400 MHz, DMSO-d6) δ(ppm): 9.11 (s, 1H); 7.76 and 7.66 (s, s, 1H); 7.43 (dd, 2H); 6.66 (dd, 2H); 4.81-4.70 (m, 1H); 3.29-3.20 (m, 1H); 3.19-3.09 (m, 1H); 2.47-2.20 (m, 2H); 2.08-1.85 (m, 2H); 1.84-1.74 (m, 1H); 1.68-1.52 (m, 1H); 1.33 and 1.08 (s, s, 9H).

Provenance & Evidence