反应详情

To a mixture of {5-bromo-2-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]-3-thienyl}(4-chlorophenyl)methanol (5.19 g, 11.4 mmol) in tetrahydrofuran (146.9 mL, 1811 mmol) was added isopropylmagnesium chloride (1M in THF, 34.2 mL, 34.2 mmol) at −40° C. under argon. After addition, the reaction temperature was raised to rt for 15 min. The mixture was then cooled to −78° C. and 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (8.149 mL, 39.94 mmol) was added. After the addition, the mixture was brought to rt. After 1 h, the mixture was heated at 75° C. overnight. The mixture was cooled to rt and quenched with saturated ammonium chloride solution. The mixture was stirred for 10 min then extracted with EtOAc. The organic layer was dried and evaporated in vacuum. The mixture was purified by chromatography to afford (4-chlorophenyl)(2-(1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophen-3-yl)methanol as a thick oil (5.32 g, 65.0%). LCMS: (FA) ES+ 502.2, 504.1.

1. additionAfter addition
2. temperatureThe mixture was then cooled to −78° C.
3. additionAfter the addition
4. customwas brought to rt
5. temperaturethe mixture was heated at 75° C. overnight
6. temperatureThe mixture was cooled to rt
7. customquenched with saturated ammonium chloride solution
8. extractionthen extracted with EtOAc
9. customThe organic layer was dried
10. customevaporated in vacuum
11. customThe mixture was purified by chromatography