反应详情

温度

-78 °C

A round bottom flask (250 mL) was charged with 6.1 g (60 mmol) of diisopropylamine dissolved in THF (100 mL). This solution was cooled to −78° C. To this was added 24 mL of 2 M butyllithium in hexane and stirred for 15 min, warmed up to 0° C. for 20 min, re-cooled to −78° C. To this was added tetrahydro-pyran-4-carboxylic acid methyl ester (7.2 g, 50 mmol) in THF (10 mL). There was almost no color change. This was stirred at −78° C. for 45 min. Then, a mixture of 5 g of HMPA and bromo-butene (8.78 g, 65 mmol) was added via cannula at −78° C. There was no noticeable change. After addition of about half of the amounts of HMPA and bromo-butene, the ice-acetone bath was removed. When the addition was complete, the flask was submerged into an ice-water bath, stirred for 20 min; and then stirred at rt for 2 h. TLC (EtOAc/Heptane 1:1, paraldehyde visualization) showed the reaction was complete. The reaction mixture was poured into ice-water (100 mL) and ether (50 mL). The two layers were separated; the aqueous layer was extracted with ether (3×50 mL). The combined organic layers were washed with brine, dried (K2CO3), filtered, and concentrated in vacuo to obtain 10.4 g (87%) of the title product as a slightly yellow liquid. The material is pure enough to be used in the next step without further purification.

1. temperaturewarmed up to 0° C. for 20 min
2. temperaturere-cooled to −78° C
3. stirringThis was stirred at −78° C. for 45 min
4. additionwas added via cannula at −78° C
5. customthe ice-acetone bath was removed
6. additionWhen the addition
7. customthe flask was submerged into an ice-water bath
8. stirringstirred for 20 min
9. stirringand then stirred at rt for 2 h
10. additionThe reaction mixture was poured into ice-water (100 mL) and ether (50 mL)
11. customThe two layers were separated
12. extractionthe aqueous layer was extracted with ether (3×50 mL)
13. washThe combined organic layers were washed with brine
14. dry with materialdried (K2CO3)
15. filtrationfiltered
16. concentrationconcentrated in vacuo