(S)-isopropyl 2-(5-bromo-4-(3-isopropylazetidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-hydroxyacetate → (S)-isopropyl 2-(5-bromo-4-(3-isopropylazetidin-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-(3-isopropylazetidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-hydroxyacetate (601 mg, 1.5 mmol) and 0.5 mL of 70% HClO4 in DCM (12 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 MgSO4. The crude product was charged (DCM) to a 40 g ISCO silica gel cartridge and gradient elution (5-50% EtOAc/hexanes) using an Isolera chromatography station gave (S)-isopropyl 2-(5-bromo-4-(3-isopropylazetidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy)acetate 621 mg (90%) as a mixture of diastereomers. 1H NMR (500 MHz, DMSO-d6) δ 5.28 (s, 1H), 5.02-4.97 (m, 1H), 4.57 (t, J=8.1 Hz, 1H), 4.40 (t, J=7.7 Hz, 1H), 4.02 (t, J=7.0 Hz, 1H), 3.91 (t, J=7.3 Hz, 1H), 2.44 (s, 3H), 2.33-2.29 (m, 1H), 2.25 (s, 3H), 1.74-1.70 (m, 1H), 1.21 (d, J=6.2 Hz, 3H), 1.17 (d, J=6.2 Hz, 3H), 1.06 (s, 9H), 0.84 (d, J=6.6 Hz, 6H). UPLC (M+H)=457.4.

Provenance & Evidence