反応 #2028906

反応方程式

2-(trans-4-propyl-cyclohexyl)-oxetane

THF

THF

2-(4′-ethoxy-2,2′,3,3′-tetrafluorobiphenyl-4-yl)acetic acid

n-butyllithium

→

3-(4′-ethoxy-2,2′,3,3′-tetrafluorobiphenyl-4-yl)-6-(4-propylcyclohexyl)tetrahydropyran-2-one

収率 87.0%

溶媒

formic acid

反応条件

後処理

1. 1
   その他prepared in the eighth step
2. 2
   workup.ADDITIONAfter the addition
3. 3
   その他was returned to room temperature
4. 4
   温度The solution was then cooled to −65° C.
5. 5
   workup.ADDITIONAfter the addition
6. 6
   その他was returned to room temperature
7. 7
   その他to give two layers
8. 8
   抽出The water layer was extracted with toluene (20 ml) three times
9. 9
   洗浄the combined organic layer was washed with water
10. 10
    乾燥dried over anhydrous magnesium sulfate
11. 11
    workup.DISTILLATIONThe solvent was distilled off under reduced pressure
12. 12
    その他The residue was purified by silica gel chromatography (silica gel: 200 g, eluent: heptane/ethyl acetate=90/10 by volume)

実験手順

THF (50 ml) was added to 2-(4′-ethoxy-2,2′,3,3′-tetrafluorobiphenyl-4-yl)acetic acid (10) (2.0 g) prepared in the eighth step. The solution was cooled to −5° C., and n-butyllithium (1.59 M in n-hexane; 7.66 ml) was added dropwise. After the addition had been completed, the reaction mixture was returned to room temperature, and the stirring was continued for 30 minutes. The solution was then cooled to −65° C., and 2-(trans-4-propyl-cyclohexyl)-oxetane (5) (1.0 g) in a THF (5 ml) solution and a boron trifluoride-diethyl ether complex (0.86 g) were added dropwise. After the addition had been completed, the reaction mixture was returned to room temperature, and a 10% aqueous solution of formic acid (100 ml) was added to give two layers. The water layer was extracted with toluene (20 ml) three times and the combined organic layer was washed with water and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography (silica gel: 200 g, eluent: heptane/ethyl acetate=90/10 by volume) to give 3-(4′-ethoxy-2,2′,3,3′-tetrafluorobiphenyl-4-yl)-6-(4-propylcyclohexyl)tetrahydropyran-2-one (11) (2.35 g) in 86.1% yield.

出典