反应详情

温度

80 °C

The diacetoxypalladium (6.11 mg, 0.027 mmol) was added to a nitrogen purged and degassed solution of (S)-isopropyl 2-(5-bromo-4-(4-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy)acetate (150 mg, 0.272 mmol), 2-(4-(4-fluorophenethoxy)phenyl)-6-methyl-1,3,6,2-dioxazaborocane-4,8-dione (111 mg, 0.299 mmol), and 2-dicyclohexylphosphino-2′,6′-dimethoxy-biphenyl (22.30 mg, 0.054 mmol), and potassium phosphate tribasic (432 mg, 2.040 mmol) in dioxane (4.5 mL) and water (0.9 mL) and stirred in a screw-capped pressure vessel for 4 h at 80° 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 (5-85% EtOAc/hexanes) using an Isolera chromatography station gave (S)-isopropyl 2-(tert-butoxy)-2-(5-(4-(4-fluorophenethoxy)phenyl)-4-(4-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl)-2,6-dimethylpyridin-3-yl)acetate 34.3 mg (18.4%) as a mixture of diastereomers. 1H NMR (500 MHz, DMSO-d6) δ 7.41-7.39 (m, 2H), 7.24-7.22 (m, 1H), 7.17-7.13 (m, 2H), 7.03 (br. s, 2H), 6.96-6.94/6.87-6.86/6.80-6.78 (series m, 1H), 5.98 (br. s, 1H), 4.95 (br. s, 1H), 4.24 (t, J=6.2 Hz, 2H), 3.99-3.96 (m, 1H), 3.08 (t, J=6.2 Hz, 2H), 3.02-2.98 (m, 1H), 2.77-2.70 (m, 1H), 2.64-2.58 (m, 1H), 2.46 (s, 3H), 2.31-2.28 (m, 1H), 2.05 (s, 3H), 2.01-1.99 (m, 1H), 1.92-1.88 (m, 1H), 1.80 (br. s, 1H), 1.62-1.47 (m, 2H), 1.23-1.17 (m, 12H), 1.14 (s, 9H). UPLC (M+H)=687.5.

1. custompurged
2. temperatureto cool
3. washthe organic layer was washed with brine
4. dry with materialdried (Na2SO4)
5. additionThe crude product was charged (DCM)
6. washto a 24 g ISCO silica gel cartridge and gradient elution (5-85% EtOAc/hexanes)