反应详情

温度

-15 °C

The 2.2 mL of benzo[d][1,3,2]dioxaborole (1.22 g, 10.2 mmol) was added to a nitrogen purged solution of isopropyl 2-(5-bromo-2,6-dimethyl-4-(4-phenylpiperidin-1-yl)pyridin-3-yl)-2-oxoacetate (2.6 g, 5.66 mmol) and 1.7 mL of (R)-1-methyl-3,3-diphenylhexahydropyrrolo[1,2-c][1,3,2]oxazaborole (471 mg, 1.7 mmol) in toluene (50 mL) at −60° C. and allowed to warm to −15° C. before being placed in the freezer overnight. The reaction was quenched with 1M Na2CO3 (15 mL), diluted with EtOAc, and stirred for 20 min. The organic layer was washed with brine and dried (MgSO4). The crude product was charged (DCM) to a 80 g ISCO silica gel cartridge and gradient elution (5-45% EtOAc/hexanes) using an Isolera chromatography station gave (S)-isopropyl 2-(5-bromo-2,6-dimethyl-4-(4-phenylpiperidin-1-yl)pyridin-3-yl)-2-hydroxyacetate 2.0 g (71%) as a mixture of diastereomers. 1H NMR (500 MHz, DMSO-d6) δ 7.34-7.29 (m, 4H), 7.22-7.19 (m, 1H), 5.95 (s, 1H), 4.99-4.94 (m, 1H), 3.78-3.75 (m, 1H), 3.51-3.47 (m, 1H), 3.04-3.02 (m, 1H), 2.90-2.87 (m, 1H), 2.66-2.61 (m, 1H), 2.54 (s, 3H), 2.41 (s, 3H), 1.87-1.72 (m, 4H), 1.14 (d, J=6.2 Hz, 3H), 1.07 (d, J=5.9 Hz, 3H). UPLC (M+H)=463.2.

1. custombefore being placed in the freezer overnight
2. customThe reaction was quenched with 1M Na2CO3 (15 mL)
3. additiondiluted with EtOAc
4. washThe organic layer was washed with brine
5. dry with materialdried (MgSO4)
6. additionThe crude product was charged (DCM)
7. washto a 80 g ISCO silica gel cartridge and gradient elution (5-45% EtOAc/hexanes)