Diisopropylamine → 4-But-3-enyl-tetrahydro-pyran-4-carboxylic acid methyl ester

Temperatur

-78 °C

In a 250 mL round bottom flask was weighed 6.1 g (60 mmol) of diisopropylamine and dissolved in THF (100 mL). This solution was cooled to −78° C. To this solution 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 mixture was added tetrahydro-pyran-4-carboxylic acid methyl ester (7.2 g, 50 mmol) in THF (10 mL). There was almost no color change (light a little bit). 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 slowly via cannula at −78° C. There was no noticeable change. When about half of this mixture was added, the dry ice-acetone bath was removed. When the addition was complete, the flask was submerged into an ice-water bath, stirred for 20 min; then 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. customIn a 250 mL round bottom flask was weighed
2. temperaturewarmed up to 0° C. for 20 min
3. temperaturere-cooled to −78° C
4. stirringThis was stirred at −78° C. for 45 min
5. additionwas added slowly via cannula at −78° C
6. additionWhen about half of this mixture was added
7. customthe dry ice-acetone bath was removed
8. additionWhen the addition
9. customthe flask was submerged into an ice-water bath
10. stirringstirred for 20 min
11. waitthen at rt for 2 h
12. additionThe reaction mixture was poured into ice-water (100 mL) and ether (50 mL)
13. customThe two layers were separated
14. extractionthe aqueous layer was extracted with ether (3×50 mL)
15. washThe combined organic layers were washed with brine
16. dry with materialdried (K2CO3)
17. filtrationfiltered
18. concentrationconcentrated in vacuo

ORD-Eintrag

ord-593a211b090042a9a34ae23eb2e5f246

Quelldatensatz

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08735385B2