反应 #1973898

反应方程式

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

收率 99.7%

溶剂

THF

ethyl acetate

THF

反应条件

后处理

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
   其他to come to 25° C
4. 4
   其他The resulting reaction mixture
5. 5
   workup.ADDITIONmixed with them
6. 6
   其他had separated into organic and aqueous phases
7. 7
   萃取the extraction into an organic phase
8. 8
   其他The resulting organic phase was separated
9. 9
   洗涤washed successively with water
10. 10
    干燥a 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

实验过程

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.

来源