Réaction #1973898

Équation de réaction

1,4-dioxaspiro[4.5]decan-8-one

HCl

3-Butoxy-1,2-difluorobenzene

n-Butyllithium

→

8-(4-butoxy-2,3-difluorophenyl)-1,4-dioxaspiro[4.5]decan-8-ol

Rendement 99.7%

Solvants

THF

ethyl acetate

THF

Conditions de réaction

Traitement

1. 1
   workup.ADDITIONwas added dropwise in the temperature range of −74° C. to −70° C.
2. 2
   workup.WAITthe stirring was continued for another 8 hours while the mixture
3. 3
   Autreto come to 25° C
4. 4
   AutreThe resulting reaction mixture
5. 5
   workup.ADDITIONmixed with them
6. 6
   Autrehad separated into organic and aqueous phases
7. 7
   Extractionthe extraction into an organic phase
8. 8
   AutreThe resulting organic phase was separated
9. 9
   Lavagewashed successively with water
10. 10
    Séchagea saturated aqueous solution of sodium hydrogencarbonate and water, and then dried over anhydrous magnesium sulfate
11. 11
    workup.DISTILLATIONThe solvent was then distilled off under reduced pressure

Mode opératoire

3-Butoxy-1,2-difluorobenzene (7) (30.0 g) and THF (500 ml) were added to a reaction vessel under an atmosphere of nitrogen, and cooled to −74° C. n-Butyllithium (1.66 M in n-hexane solution; 120 ml) was added dropwise in the temperature range of −74° C. to −70° C. and the stirring was continued for another 2 hours. Successively, 1,4-dioxaspiro[4.5]decan-8-one (8) (30.2 g) in THF (200 ml) solution was added dropwise in the temperature range of −75° C. to −70° C., and the stirring was continued for another 8 hours while the mixture was allowed to come to 25° C. The resulting reaction mixture was poured into a 1N—HCl aqueous solution (500 ml) and ethyl acetate (500 ml) in a vessel and mixed with them. The mixture was then allowed to stand until it had separated into organic and aqueous phases, and the extraction into an organic phase was carried out. The resulting organic phase was separated, and washed successively with water, a saturated aqueous solution of sodium hydrogencarbonate and water, and then dried over anhydrous magnesium sulfate. The solvent was then distilled off under reduced pressure to leave 8-(4-butoxy-2,3-difluorophenyl)-1,4-dioxaspiro[4.5]decan-8-ol (9) (55.0 g). The resulting compound (9) was a pale yellow oil.

Source