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

Participants

Reaction Conditions

Reaction Steps

The Pd(Ph3P)4 (33.5 mg, 0.029 mmol) was added to a nitrogen purged and degassed solution of (S)-isopropyl 2-(5-bromo-2,6-dimethyl-4-(4-phenylpiperidin-1-yl)pyridin-3-yl)-2-(tert-butoxy)acetate (150 mg, 0.29 mmol), (4-(4-fluorophenethoxy)phenyl)boronic acid (83 mg, 0.32 mmol), and sodium carbonate (184 mg, 1.74 mmol) in dioxane (4.5 mL) and water (0.9 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-(5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethyl-4-(4-phenylpiperidin-1-yl)pyridin-3-yl)acetate 98 mg (52%) as a mixture of diastereomers. 1H NMR (500 MHz, DMSO-d6) δ 7.42-7.39 (m, 2H), 7.29-7.23 (m, 3H), 7.17-7.13 (m, 5H), 7.06-7.02 (m, 3H), 6.07 (s, 1H), 4.98-4.93 (m, 1H), 4.25 (t, J=7.0 Hz, 2H), 3.08 (t, J=6.2 Hz, 2H), 2.78-2.72 (m, 1H), 2.62-2.58 (m, 1H), 2.47 (br. s, 1H), 2.46 (s, 3H), 2.28 (br. s, 1H), 2.05 (s, 3H), 1.94-1.90 (m, 1H), 1.77-1.66 (m, 2H), 1.57 (br. s, 2H), 1.18 (br. s, 12H), 1.14 (d, J=5.5 Hz, 3H). UPLC (M+H)=653.5.

Provenance & Evidence