反应详情
EQUATION
反应方程式
REACTANTS
反应物
PRODUCTS
生成物
AUXILIARIES
试剂、催化剂与溶剂
CONDITIONS
反应条件
- 温度
- 100 °C
PROCEDURE
实验过程
A 20-mL vial was charged with 9-(((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-2-piperazinyl)methyl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-ol (endo) and 9-(((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-2-piperazinyl)methyl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-one (0.53 g, 1.9 mmol), Hünig's base (0.67 mL, 3.8 mmol), 2-(2-chloropyrimidin-5-yl)-1,1,1,3,3,3-hexafluoropropan-2-ol (0.53 g, 1.88 mmol, Intermediate D) and dioxane (10 mL). The vial was, sealed and heated at 100° C. overnight. The crude reaction was concentrated onto silica gel and purified via column chromatography (40 g silica gel, 0 to 100% EtOAc in hexanes) to give 9-(((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-ol (endo) and 9-(((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-one (0.46 g) as a 1:1 mixture.
WORKUP
后处理
- customsealed
- customThe crude reaction
- concentrationwas concentrated onto silica gel
- custompurified via column chromatography (40 g silica gel, 0 to 100% EtOAc in hexanes)