(S)-isopropyl 2-(5-bromo-4-(4-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-hydroxyacetate → (S)-isopropyl 2-(5-bromo-4-(4-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl)-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-(5-bromo-4-(4-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-hydroxyacetate (540 g, 1.1 mmol) and 0.15 mL of 70% HClO4 in DCM (8 mL) for 20 min. The reaction mixture was allowed to warm to rt and stirred for 18 h in a pressure sealed vessel, diluted with DCM, washed with 1M Na2CO3 solution, and dried over Na2SO4. The crude product was charged (DCM) to a 40 g ISCO silica gel cartridge and gradient elution (5-65% EtOAc/hexanes) using an Isolera chromatography station gave (S)-isopropyl 2-(5-bromo-4-(4-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy)acetate 469 mg (78%) as a mixture of diastereomers. 1H NMR (500 MHz, DMSO-d6) δ 6.15 (br. s, 1H), 4.94-4.89 (m, 1H), 3.94-3.90 (m, 1H), 3.21-3.13 (m, 1H), 3.11-3.01 (m, 2H), 2.93-2.78 (m, 1H), 2.53 (s, 3H), 2.43 (s, 3H), 2.17-2.02 (m, 3H), 1.90-1.82 (m, 2H), 1.26 (d, J=7.0 Hz, 6H), 1.16-1.14 (m, 12H), 1.07 (d, J=5.9 Hz, 3H). UPLC (M+H)=553.2.

Provenance & Evidence