反应详情

温度

-70 °C

To a solution of 2-bromo-1-fluoro-4-methylbenzene (0.76 g, 4 mmol) in THF (15 ml) at −70° C. under Ar a solution of n-BuLi (1.6 M in hexane, 2.5 ml, 4 mmol) was added dropwise. The reaction mixture was stirrred at −70° C. for 1 h, then BF3.Et2O (0.5 ml, 4 mmol) was added. After stirring for 20 min at −70° C., a solution of 6-benzyl-1-oxa-6-azaspiro[2.5]octane (0.41 g, 2 mmol) in dry THF (5 ml) was added dropwise. The stirring was continued for 2 h at −70° C., then the reaction mixture was quenched with sat. aq. NH4Cl (20 ml). The layers were separated, the aqueous layer extracted with THF. The combined organic layers were dried over Na2SO4. The solvent was removed in vacuo. Diethyl ether (50 ml) was added to the residue, folowed by a 2 M HCl in Et2O (5 ml). The precipitate was collected, washed with Et2O, and dissolved in minimal volume of methanol (ca. 5 ml). Water (50 ml) was added, and pH adjusted to 10 by addition of 2 M aq. NaOH. The mixture was extracted with ethyl acetate (2×25 ml), and the combined organic extracts were dried with Na2SO4. Evaporation of solvent afforded brownish oil.

1. waitThe stirring was continued for 2 h at −70° C.
2. customthe reaction mixture was quenched with sat. aq. NH4Cl (20 ml)
3. customThe layers were separated
4. extractionthe aqueous layer extracted with THF
5. dry with materialThe combined organic layers were dried over Na2SO4
6. customThe solvent was removed in vacuo
7. additionDiethyl ether (50 ml) was added to the residue
8. customThe precipitate was collected
9. washwashed with Et2O
10. dissolutiondissolved in minimal volume of methanol (ca. 5 ml)
11. additionWater (50 ml) was added
12. additionpH adjusted to 10 by addition of 2 M aq. NaOH
13. extractionThe mixture was extracted with ethyl acetate (2×25 ml)
14. dry with materialthe combined organic extracts were dried with Na2SO4
15. customEvaporation of solvent
16. customafforded brownish oil