Sodium Bicarbonate → {4-[(2R)-2-Hydroxy-2-(4-hydroxy-3-methanesulfonylamino-phenyl)-ethylamino]-piperidin-1-yl}-benzoic acid ethyl ester

Participants

Reaction Steps

1-(4-Ethoxycarbonylphenyl)-4-piperidone (Taylor, E. C., Skotnicki, J. S. Synthesis, 1981, 606) (29 g, 1.2 mmol) and N-[5-(2-amino-(1R)-1-hydroxy-ethyl)-2-hydroxy-phenyl]-methanesulfonamide (which was obtained in Example 10) (0.29 g, 1.2 mmol) were mixed in dimethylformamide (10 mL) and then treated with sodium triacetoxyborohydride (1.01 g, 4.7 mmol) and acetic acid (0.5 mL). After stirring at room temperature under a nitrogen atmosphere for 15 hours the mixture was poured into a saturated aqueous sodium bicarbonate. The precipitate which was formed was collected and purified by silica gel chromatography (methanol/methylene chloride) to give the titled compound as a white solid (0.28 g, 50%); mp>95° C. (decomposed); 1H NMR (300 MHz, DMSO-d6) δ 1.28 (t, J=7.1 Hz, 3 H), 1.30–1.55 (m, 2 H), 1.80–1.95 (m, 2 H), 2.55–3.50 (m, 5 H), 2.92 (s, 3 H), 3.75–3.90 (m, 2 H), 4.22 (q, J=7.1 Hz, 2 H), 6.82 (d, J=8.2 Hz, 1 H), 6.95 (d, J=8.9 Hz, 2 H), 7.00 (dd, J=8.2, 1.9 Hz, 1 H), 7.18 (d, J=1.9 Hz, 1 H), 7.75 (d, J=8.9 Hz, 2 H); MS (ES) m/z: 478.0 (MH+); HRMS Calcd. for C23H32N3O6S(MH+): 478.2006. Found: 478.2000.

Provenance & Evidence