Acetic Acid → Methyl (5R)-5-(5-{[(2-fluorophenyl)methyl]oxy}-2-pyridinyl)-L-prolinate

Participants

Reaction Steps

To a solution of methyl (2S)-5-(5-{[(2-fluorophenyl)methyl]oxy}-2-pyridinyl)-3,4-dihydro-2H-pyrrole-2-carboxylate (D85, 300 mg, 0.91 mmol) in ethyl acetate was added platinum on activated carbon (70 mg, 5 wt. % dry basis Degussa type F101 RAW) and the mixture was stirred under hydrogen atmosphere (P=1 atm) for 4 hours. After a further addiction of acetic acid (0.4 ml) and stirring for 12 hours the reaction wasn't complete. A further addiction of catalyst (70 mg) and trifluoroacetic acid was required before the reaction was complete. The catalyst was filtered off, the solvent removed under reduced pressure and the residue filtered on scx cartridge. The residue was purified by chromatography on silica gel using cyclohexane/ethyl acetate (7:3 to 6:4) to afford the title compound as a colourless oil (180 mg, 60%). Rt (HPLC): 3.69 min; MS: (ES/+) m/z: 331 [MH]+ C18H19FN2O3 requires 330; 1H NMR (400 MHz, CDCl3) δ (ppm): 8.27-8.43 (m, 1H); 7.45-7.56 (m, 1H); 7.38-7.44 (m, 1H); 7.31-7.38 (m, 1H); 7.24-7.31 (m, 1H); 7.15-7.23 (m, 1H); 7.08-7.15 (m, 1H); 5.18 (s, 2H); 4.32-4.41 (m, 1H); 3.98-4.05 (m, 1H); 3.79 (s, 3H); 2.19-2.31 (m, 2H); 2.04-2.13 (m, 1H); 1.77-1.90 (m, 1H).

Provenance & Evidence