Sodium Carbonate → (S)-isopropyl 2-(tert-butoxy)-2-(4-(3,3-dimethylazetidin-1-yl)-5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethylpyridin-3-yl)acetate

Participants

Reaction Conditions

Reaction Steps

The Pd(Ph3P)4 (57.6 mg, 0.05 mmol) was added to a nitrogen purged and degassed solution of (S)-isopropyl 2-(5-bromo-4-(3,3-dimethylazetidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy)acetate (110 mg, 0.25 mmol), (4-(4-fluorophenethoxy)phenyl)boronic acid (71.3 mg, 0.27 mmol), and sodium carbonate (185 mg, 1.74 mmol) in dioxane (3 mL) and water (0.6 mL) and stirred in a screw-capped pressure vessel for 4 h at 90° C. The reaction was allowed to cool, diluted with EtOAc, and the organic layer was washed with brine and dried (Na2SO4). The crude product was charged (DCM) to a 24 g ISCO silica gel cartridge and gradient elution (5-65% EtOAc/hexanes) using an Isolera chromatography station gave (S)-isopropyl 2-(tert-butoxy)-2-(4-(3,3-dimethylazetidin-1-yl)-5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethylpyridin-3-yl)acetate 97 mg (67.5%). 1H NMR (500 MHz, DMSO-d6) δ 7.40-7.37 (m, 2H), 7.32 (br. s, 1H), 7.14 (t, J=8.4 Hz, 2H), 6.99 (d, J=8.1 Hz, 1H), 6.93 (d, J=8.1 Hz, 1H), 6.78 (br. s, 1H), 5.20 (s, 1H), 5.02-4.97 (m, 1H), 4.20 (t, J=6.2 Hz, 2H), 3.44 (s, 4H), 3.05 (t, J=6.6 Hz, 2H), 1.99 (s, 3H), 1.89 (s, 3H), 1.21-1.18 (m, 6H), 1.11 (s, 9H), 1.02 (s, 6H). UPLC (M+H)=577.5.

Provenance & Evidence