HCID 118307773, compound → HCID 118307732, compound

Participants

Reaction Steps

The isobutylene gas was bubbled into a nitrogen purged, cooled (0° C.) solution of (S)-isopropyl 2-(5-bromo-4-(4-ethyl-4-methylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-hydroxyacetate (1.9 g, 4.19 mmol) and 0.6 mL of 70% HClO4 in DCM (15 mL) for 20 min. The reaction mixture was allowed to warm to rt and stirred for 18 h in a pressure sealed vessel, after which it was recooled, and an additional 0.4 mL of 70% HClO4 was added at 0° C., and the reaction was stirred for 24 h at rt. The reaction was 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 (5-12% EtOAc/hexanes) using an Isolera chromatography station gave (S)-isopropyl 2-(5-bromo-4-(4-ethyl-4-methylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy)acetate 1.67 g (64%) as a mixture of diastereomers. 1H NMR (500 MHz, DMSO-d6) 6 (br. s, 1H), 4.94-4.89 (m, 1H), 3.98 (br. s, 1H), 3.45-3.39 (m, 2H), 2.82 (m, 1H), 2.53 (s, 3H), 2.42 (s, 3H), 1.53-1.43 (m, 4H), 1.32-1.26 (m, 2H), 1.14 (br. s, 12H), 1.07 (d, J=6.2 Hz, 3H), 0.99/0.91 (s, 3H), 0.8 (t, J=7.3 Hz, 3H). UPLC (M+H)=485.4.

Provenance & Evidence