반응 #167526

반응 방정식

HCl

ethyl bromodifluoroacetate

THF

4′-propyl-[1,1′-bi(cyclohexane)]-4-carboaldehyde

THF

→

ethyl 2,2-difluoro-3-hydroxy-3-(4′-propyl-[1,1′-bi(cyclohexane)]-4-yl)propanoate

수율 54.8%

용매

ethyl acetate

반응 조건

후처리

1. 1
   온도to heating
2. 2
   온도reflux for 4 hours
3. 3
   온도After cooling the resultant
4. 4
   기타reaction mixture to 25° C.
5. 5
   기타to separate the mixture into an organic layer
6. 6
   기타The resultant organic layer was isolated
7. 7
   세척washed with water
8. 8
   건조a saturated aqueous solution of sodium hydrogencarbonate and water, and then the resultant solution was dried over anhydrous magnesium sulfate
9. 9
   workup.DISTILLATIONThen, the solvent was distilled off under reduced pressure
10. 10
    기타the resultant residue was purified by a preparative isolation operation by means of column chromatography
11. 11
    건조ethyl acetate=9:1 in a volume ratio) as an eluent and silica gel as a filler, the resultant product was dried

실험 절차

To a reaction vessel under a nitrogen atmosphere, 10.7 g of well-dried zinc, 25.0 g of ethyl bromodifluoroacetate (e-14) and 25 ml of THF were added, and the resultant mixture was cooled to 0° C. and stirred for 1 hour. The solution was slowly added dropwise in a temperature range of 20° C. to 25° C. to another reaction vessel under a nitrogen atmosphere in which 19.4 g of 4′-propyl-[1,1′-bi(cyclohexane)]-4-carboaldehyde (e-1) and 100 ml of THF were put, and the resultant mixture was further subjected to heating reflux for 4 hours. After cooling the resultant reaction mixture to 25° C., 300 ml of 1 N HCl aqueous solution and 300 ml of ethyl acetate were added to separate the mixture into an organic layer and an aqueous layer, and an extraction operation was performed. The resultant organic layer was isolated, and washed with water, a saturated aqueous solution of sodium hydrogencarbonate and water, and then the resultant solution was dried over anhydrous magnesium sulfate. Then, the solvent was distilled off under reduced pressure, the resultant residue was purified by a preparative isolation operation by means of column chromatography using a mixed solvent of toluene and ethyl acetate (toluene:ethyl acetate=9:1 in a volume ratio) as an eluent and silica gel as a filler, the resultant product was dried, and thus 16.2 g of ethyl 2,2-difluoro-3-hydroxy-3-(4′-propyl-[1,1′-bi(cyclohexane)]-4-yl)propanoate (e-15) was obtained. A yield based on compound (e-1) was 54.8%.

출처