Reaction #67985

Reaction equation

benzyl 2-bromoethyl ether

diisopropylamine

butyllithium hexane

citric acid

1,4-dioxaspiro[4.5]decane-8-carbonitrile

→

8-(2-(benzyloxy)ethyl)-1,4-dioxaspiro[4.5]decane-8-carbonitrile

Solvents

tetrahydrofuran

tetrahydrofuran

ethyl acetate

Conditions

Workup

1. 1
   workup.ADDITIONwas added dropwise at −78° C.
2. 2
   workup.STIRRINGAfter stirring at −78° C. for 1 hour
3. 3
   workup.STIRRINGfurther stirred for 1 hour
4. 4
   OtherThe organic layer was separated
5. 5
   Extractionthe aqueous layer was extracted with ethyl acetate
6. 6
   Washthe resultant solution was washed with an aqueous saturated sodium chloride solution
7. 7
   Dryingdried over anhydrous magnesium sulfate
8. 8
   Otherthe solvent was removed under reduced pressure
9. 9
   OtherThe residue thus obtained
10. 10
    Otherwas purified by silica gel column chromatography [eluent; hexane:ethyl acetate=6:1]

Procedure

To 8 mL of a tetrahydrofuran solution containing 0.94 mL of diisopropylamine, 4.5 mL of 1.6 mol/L butyllithium/hexane was added dropwise at −78° C., the mixture was stirred at the same temperature for 1 hour, and then thereto was added dropwise 7 mL of a tetrahydrofuran solution containing 0.60 g of 1,4-dioxaspiro[4.5]decane-8-carbonitrile. After stirring at −78° C. for 1 hour, the mixture was added dropwise with 0.85 mL of benzyl 2-bromoethyl ether, and further stirred for 1 hour. The temperature of the reaction mixture was increased to room temperature, and then a 10% aqueous citric acid solution and ethyl acetate were added thereto. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layer and the extract were combined, the resultant solution was washed with an aqueous saturated sodium chloride solution and then dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue thus obtained was purified by silica gel column chromatography [eluent; hexane:ethyl acetate=6:1] to obtain 1.1 g of a colorless oily substance, 8-(2-(benzyloxy)ethyl)-1,4-dioxaspiro[4.5]decane-8-carbonitrile.

Source