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

Participants

Reaction Conditions

Reaction Steps

The Pd(Ph3P)4 (38.1 mg, 0.033 mmol) was added to a nitrogen purged and degassed solution of (S)-isopropyl 2-(5-bromo-4-(3-isopropylazetidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy)acetate (150 mg, 0.33 mmol), (4-(4-fluorophenethoxy)phenyl)boronic acid (94 mg, 0.36 mmol), and sodium carbonate (209 mg, 1.98 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 (5-75% EtOAc/hexanes) using an Isolera chromatography station gave (S)-isopropyl 2-(tert-butoxy)-2-(5-(4-(4-fluorophenethoxy)phenyl)-4-(3-isopropylazetidin-1-yl)-2,6-dimethylpyridin-3-yl)acetate 152 mg (78%) as a mixture of diastereomers. 1H NMR (500 MHz, DMSO-d6) δ 7.39-7.36 (m, 2H), 7.31-7.30 (m, 1H), 7.14 (t, J=8.8 Hz, 2H), 7.00 (d, J=8.8 Hz, 1H), 6.94 (d, J=8.4 Hz, 1H), 6.82-6.80 (m, 1H), 5.18 (s, 1H), 5.03-4.98 (m, 1H), 4.21 (t, J=6.6 Hz, 2H), 3.43-3.25 (series m, 4H), 3.05 (t, J=6.6 Hz, 2H), 2.27 (s, 3H), 2.01 (s, 3H), 2.01-1.98 (m, 1H), 1.48-1.44 (m, 1H), 1.21-1.19 (m, 6H), 1.10 (s, 9H), 0.68 (d, J=6.6 Hz, 3H), 0.63 (d, J=6.6 Hz, 3H). UPLC (M+H)=591.6.

Provenance & Evidence