Reaktion #44500

Reaktionsgleichung

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

Lösungsmittel

tetrahydrofuran

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

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONAfter the addition
2. 2
   workup.STIRRINGstirred for another five hours
3. 3
   TemperaturThe dark brown reaction mixture was cooled (0° C.)
4. 4
   Sonstigequenched with acetic acid (0.1 mL)
5. 5
   Sonstigepartitioned with diethyl ether and water
6. 6
   WaschenThe organic phase was washed with water and brine
7. 7
   Trocknendried (MgSO4)
8. 8
   Filtrationfiltered
9. 9
   Sonstigeevaporated
10. 10
    SonstigeThe residue was purified over silica gel using 5-80% ethyl acetate in hexanes

Vorschrift

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.

Quelle