(S)-isopropyl 2-(5-bromo-2,6-dimethyl-4-(4-methylpiperidin-1-yl)pyridin-3-yl)-2-hydroxyacetate → (S)-isopropyl 2-(5-bromo-2,6-dimethyl-4-(4-methylpiperidin-1-yl)pyridin-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-(5-bromo-2,6-dimethyl-4-(4-methylpiperidin-1-yl)pyridin-3-yl)-2-hydroxyacetate (2.25 g, 5.63 mmol) and 0.53 mL of 70% HClO4 in DCM (30 mL) for 20 min. The reaction mixture was allowed to warm to rt and stirred for 72 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 (0-12% EtOAc/hexanes) using an Isolera chromatography station gave (S)-isopropyl 2-(5-bromo-2,6-dimethyl-4-(4-methylpiperidin-1-yl)pyridin-3-yl)-2-(tert-butoxy)acetate 1.82 g (71%) as a mixture of diastereomers. 1H NMR (500 MHz, DMSO-d6) δ 6.16 (s, 1H), 4.93-4.90 (m, 1H), 3.82-3.77 (m, 1H), 3.24 (t, J=10.6 Hz 1H), 2.98 (d, J=9.9 Hz, 1H), 2.74 (br. s, 1H), 2.51 (s, 3H), 2.41 (s, 3H), 1.73 (br. s, 1H), 1.62 (br. s, 1H), 1.49 (br. s, 1H), 1.28-1.23 (m, 2H), 1.16-1.14 (m, 12H), 1.07 (d, J=6.2 Hz, 3H), 0.97 (d, J=6.2 Hz, 3H). UPLC (M+H)=457.3.

Provenance & Evidence