反应 #44500

反应方程式

product

9-(4-Hydroxymethyl-3,3-dimethyl-2-oxo-pyrrolidin-1-yl)-bicyclo[3.3.1]nonane-3-carboxylic acid methyl ester

6-chloro-nicotinonitrile

NaH

→

titled product

9-[4-(5-Cyano-pyridin-2-yloxymethyl)-3,3-dimethyl-2-oxo-pyrrolidin-1-yl]-bicyclo[3.3.1]nonane-3-carboxylic acid methyl ester

溶剂

tetrahydrofuran

1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone

反应条件

后处理

1. 1
   workup.ADDITIONAfter the addition
2. 2
   workup.STIRRINGstirred for another five hours
3. 3
   温度The dark brown reaction mixture was cooled (0° C.)
4. 4
   其他quenched with acetic acid (0.1 mL)
5. 5
   其他partitioned with diethyl ether and water
6. 6
   洗涤The organic phase was washed with water and brine
7. 7
   干燥dried (MgSO4)
8. 8
   过滤filtered
9. 9
   其他evaporated
10. 10
    其他The residue was purified over silica gel using 5-80% ethyl acetate in hexanes

实验过程

NaH (0.1 g, 60% in oil, 2.56 mmol) was added in one portion to a stirred and cooled (0° C.) solution of the product of Example 7D (0.48 g, 1.42 mmol) and 6-chloro-nicotinonitrile (0.35 g, 2.56 mmol) in tetrahydrofuran (7 ml) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (7 mL). After the addition, the solution was warmed to room temperature and stirred for another five hours. The dark brown reaction mixture was cooled (0° C.), quenched with acetic acid (0.1 mL), and partitioned with diethyl ether and water. The organic phase was washed with water and brine, dried (MgSO4), filtered, and evaporated. The residue was purified over silica gel using 5-80% ethyl acetate in hexanes to give the titled product as a solid.

来源