反应详情

To a reaction vessel under a nitrogen atmosphere, 1.7 g of well-dried zinc, 3.6 g of ethyl bromofluoroacetate (e-2) and 10 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 2.0 g of 4-propylcyclohexane carboaldehyde (e-8) and 10 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., 100 ml of 1 N HCl aqueous solution and 100 ml of ethyl acetate were added to separate the mixture into an organic layer and an aqueous layer, and an extraction operation was performed. Then, 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 3.8 g of ethyl 2-fluoro-3-hydroxy-3-(4-propylcyclohexyl)propanoate (e-9) was obtained.

1. temperatureto heating
2. temperaturereflux for 4 hours
3. temperatureAfter cooling the resultant
4. customreaction mixture to 25° C.
5. customto separate the mixture into an organic layer
6. customThen, the resultant organic layer was isolated
7. washwashed with water
8. dry with materiala saturated aqueous solution of sodium hydrogencarbonate and water, and then the resultant solution was dried over anhydrous magnesium sulfate
9. distillationThen, the solvent was distilled off under reduced pressure
10. customthe resultant residue was purified by a preparative isolation operation by means of column chromatography
11. dry with materialethyl acetate=9:1 in a volume ratio) as an eluent and silica gel as a filler, the resultant product was dried