Potassium Phosphate, Tribasic → (S)-isopropyl 2-(tert-butoxy)-2-(5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethyl-4-(4-methylpiperidin-1-yl)pyridin-3-yl)acetate

Participants

Reaction Conditions

Reaction Steps

Pd(Ph3P)4 (76 mg, 0.066 mmol) was added to an argon-degassed solution of (S)-isopropyl 2-(5-bromo-2,6-dimethyl-4-(4-methylpiperidin-1-yl)pyridin-3-yl)-2-(tert-butoxy)acetate (150 mg, 0.329 mmol), 2-(4-(4-fluorophenethoxy)phenyl)-6-methyl-1,3,6,2-dioxazaborocane-4,8-dione (94 mg, 0.362 mmol), potassium phosphate tribasic (524 mg, 2.47 mmol) in dioxane (2 ml) and water (0.5 ml) stirred in a screw-capped pressure vessel for 16 h at 80° C. The reaction was allowed to cool, diluted with EtOAc, and the organic layer was washed with brine and dried (MgSO4). The crude product was charged (DCM) to a 40 g ISCO silica gel cartridge and gradient elution (0-20% EtOAc/hexanes) using an Isolera chromatography station gave (S)-isopropyl 2-(tert-butoxy)-2-(5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethyl-4-(4-methylpiperidin-1-yl)pyridin-3-yl)acetate 139 mg (72%) as a mixture of diastereomers. 1H NMR (500 MHz, DMSO-d6) δ 7.44-7.38 (m, 2H), 7.20 (d, J=7.3 Hz, 1H), 7.15 (t, J=8.8 Hz, 2H), 7.03-6.94 (m, 3H), 5.97 (br. s, 1H), 4.96 (dt, J=12.3, 6.3 Hz, 1H), 4.23 (t, J=6.6 Hz, 2H), 3.36-3.29 (m, 4H), 3.07 (t, J=6.6 Hz, 2H), 2.43 (s, 3H), 2.04 (s, 3H), 1.75 (t, J=11.4 Hz, 1H), 1.52-1.47 (m, 1H), 1.37 (br. s, 1H), 1.19 (d, J=6.2 Hz, 3H), 1.15-1.13 (m, 12H), 1.08-1.02 (m, 2H), 0.84 (d, J=5.1 Hz, 3H). UPLC (M+H)=591.56.

Provenance & Evidence