Реакция #44500

Уравнение реакции

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

Растворители

tetrahydrofuran

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

Условия реакции

Обработка

1. 1
   workup.ADDITIONAfter the addition
2. 2
   workup.STIRRINGstirred for another five hours
3. 3
   ТемператураThe dark brown reaction mixture was cooled (0° C.)
4. 4
   Другоеquenched with acetic acid (0.1 mL)
5. 5
   Другоеpartitioned with diethyl ether and water
6. 6
   ПромывкаThe organic phase was washed with water and brine
7. 7
   Сушкаdried (MgSO4)
8. 8
   Фильтрацияfiltered
9. 9
   Другоеevaporated
10. 10
    ДругоеThe residue was purified over silica gel using 5-80% ethyl acetate in hexanes

Методика

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.

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