Reacción #44500

Ecuación de reacción

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

Disolventes

tetrahydrofuran

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

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITIONAfter the addition
2. 2
   workup.STIRRINGstirred for another five hours
3. 3
   TemperaturaThe dark brown reaction mixture was cooled (0° C.)
4. 4
   Otroquenched with acetic acid (0.1 mL)
5. 5
   Otropartitioned with diethyl ether and water
6. 6
   LavadoThe organic phase was washed with water and brine
7. 7
   Secadodried (MgSO4)
8. 8
   Filtraciónfiltered
9. 9
   Otroevaporated
10. 10
    OtroThe residue was purified over silica gel using 5-80% ethyl acetate in hexanes

Procedimiento

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.

Fuente