反应详情

Methyl (2-trifluoromethylphenyl)acetate (5.0 g) was dissolved in tetrahydrofuran (10 mL), and the solution was added at −78° C. to a solution containing potassium bistrimethylsilylamide (50 mL) in tetrahydrofuran (190 mL). After stirring for 30 minutes, epibromohydrin (1.96 mL) was added at the same temperature. After further 10 minutes, a boron trifluoride-diethyl ether complex (3.16 mL) was added. After stirring at −78° C. for one hour, the reaction was terminated with a saturated sodium bicarbonate aqueous solution. The organic layer diluted with ethyl acetate was washed with a saturated sodium bicarbonate aqueous solution and brine and dried over magnesium sulfate. Concentration under reduced pressure gave a residue which was dissolved in methanol (50 mL) and methylene chloride (50 mL) and treated with potassium carbonate (15.8 g). After one hour, potassium carbonate was precipitated by adding methylene chloride (200 mL) and removed by filtration through celite. The resulting solution was washed with saturated ammonium chloride aqueous solution and brine and dried over magnesium sulfate. Concentration under reduced pressure gave a crude product. The crude product was purified by silica gel column chromatography (mobile phase:ethyl acetate/heptane=0 to 30%) to obtain a diastereomer mixture (2.61 g).

1. additionthe solution was added at −78° C. to a solution
2. waitAfter further 10 minutes
3. additiona boron trifluoride-diethyl ether complex (3.16 mL) was added
4. stirringAfter stirring at −78° C. for one hour
5. customthe reaction was terminated with a saturated sodium bicarbonate aqueous solution
6. additionThe organic layer diluted with ethyl acetate
7. washwas washed with a saturated sodium bicarbonate aqueous solution and brine
8. dry with materialdried over magnesium sulfate
9. concentrationConcentration under reduced pressure
10. customgave a residue which
11. waitAfter one hour
12. custompotassium carbonate was precipitated
13. additionby adding methylene chloride (200 mL)
14. customremoved by filtration through celite
15. washThe resulting solution was washed with saturated ammonium chloride aqueous solution and brine
16. dry with materialdried over magnesium sulfate
17. concentrationConcentration under reduced pressure
18. customgave a crude product
19. customThe crude product was purified by silica gel column chromatography (mobile phase:ethyl acetate/heptane=0 to 30%)