反应详情

Flush with nitrogen a 12 L 3-neck round bottom flask equipped with mechanical stirrer, internal temperature probe/N2 inlet, and 1 L addition funnel for 20 min, then add (R)-4-benzyl-2-oxazolidinone (250 g, 1.41 mol). Dilute with THF (1.8 L) and cool in a dry ice/acetone bath until the internal temperature is −74° C. Transfer a 1.6M hexanes solution of n-butyllithium (970 mL, 1.552 mol) to the addition funnel via cannula, and add to the oxazolidinone solution at a rate such that the internal temperature does not reach above −65° C. After the addition is complete, allow the reaction to stir in the cooling bath 30 min. Transfer 4-pentenoyl chloride (175 mL, 1.585 mol) to the addition funnel and add dropwise to the anion solution over a 25 min period. Stir the reaction for 45 min in the cooling bath. Remove the cooling bath and stir the reaction 18 hr as it slowly reaches room temperature. Dilute the mixture with 1N aqueous hydrochloric acid (1.5 L) and diethyl ether (1.0 L). Separate the layers and wash the organic phase with water (2×1 L) then brine (1 L). Extract the combined aqueous washes with ether (1 L). Dry the combined organic phases over anhydrous magnesium sulfate, filter, and concentrate to 390 g of a tan oil. Purify this material by silica gel chromatography using hexanes:ethyl acetate to obtain 345 g (94.5%) of a clear, yellow oil.

1. customFlush with nitrogen a 12 L 3-neck round bottom flask
2. customequipped with mechanical stirrer
3. additioninternal temperature probe/N2 inlet, and 1 L addition funnel for 20 min
4. temperaturecool in a dry ice/acetone bath until the internal temperature
5. customis −74° C
6. customdoes not reach above −65° C
7. additionAfter the addition
8. customthe reaction
9. stirringStir
10. customthe reaction for 45 min in the cooling bath
11. customRemove the cooling bath
12. stirringstir
13. customthe reaction 18 hr as it slowly reaches room temperature
14. customSeparate the layers
15. washwash the organic phase with water (2×1 L)
16. extractionExtract the combined aqueous washes with ether (1 L)
17. dry with materialDry the combined organic phases over anhydrous magnesium sulfate
18. filtrationfilter
19. concentrationconcentrate to 390 g of a tan oil
20. customPurify this material by silica gel chromatography
21. customethyl acetate to obtain 345 g (94.5%) of a clear, yellow oil