반응 #2028906

반응 방정식

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

수율 87.0%

용매

formic acid

반응 조건

후처리

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

실험 절차

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.

출처