(S)-isopropyl 2-(4-(4-benzylpiperidin-1-yl)-5-bromo-2,6-dimethylpyridin-3-yl)-2-hydroxyacetate → (S)-isopropyl 2-(4-(4-benzylpiperidin-1-yl)-5-bromo-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy)acetate

Participants

Reaction Steps

The isobutylene gas was bubbled into a nitrogen purged, cooled (0° C.) solution of (S)-isopropyl 2-(4-(4-benzylpiperidin-1-yl)-5-bromo-2,6-dimethylpyridin-3-yl)-2-hydroxyacetate (1.35 g, 2.84 mmol) and 0.27 mL of 70% HClO4 in DCM (25 mL) for 20 min. The reaction mixture was allowed to warm to rt and stirred for 48 h in a pressure sealed vessel. The reaction was then diluted with DCM, washed with 1M Na2CO3 solution, and dried over MgSO4. The crude product was charged (DCM) to a 80 g ISCO silica gel cartridge and gradient elution (0-25% EtOAc/hexanes) using an Isolera chromatography station gave (S)-isopropyl 2-(4-(4-benzylpiperidin-1-yl)-5-bromo-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy)acetate 1.27 g (84%) as a mixture of diastereomers. 1H NMR (500 MHz, DMSO-d6) δ 7.30-7.27 (m, 2H), 7.20-7.18 (m, 3H), 6.12 (br. s, 1H), 4.93-4.88 (m, 1H), 3.79-3.74 (m, 1H), 3.20 (t, J=12.5 Hz, 1H), 2.97-2.95 (m, 1H), 2.74 (br. s, 1H), 2.60 (d, J=5.1 Hz, 2H), 2.51 (s, 3H), 2.40 (s, 3H), 1.68 (br. s, 2H), 1.60-1.57 (m, 1H), 1.36-1.29 (m, 2H), 1.18 (d, J=6.2 Hz, 3H), 1.11 (s, 9H), 1.06 (d, J=6.2 Hz, 3H). UPLC (M+H)=533.3.

Provenance & Evidence