Diisopropylamine → 1-tert-Butyl 4-ethyl 4-(prop-2-en-1-yl)piperidine-1,4-dicarboxylate

Temperature

-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 was added 24 mL of 2.5 M (60 mmol) of 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 piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester (12.87 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 10.92 g of allyl iodide was added via cannula. The mixture was clear, very light yellow solution. This mixture was stirred at −78° C. for 20 min, then, the dry ice bath was removed and the stirring was continued to allow the reaction mixture to warm up to r.t. over 40 min. The reaction mixture was poured into a mixture of ice (˜50 g), aq. saturated NH4Cl solution (50 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 15 g (100%) of the title compound as a yellow liquid,

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 via cannula
6. stirringThis mixture was stirred at −78° C. for 20 min
7. customthe dry ice bath was removed
8. temperatureto warm up to r.t. over 40 min
9. additionThe reaction mixture was poured into a mixture of ice (˜50 g), aq. saturated NH4Cl solution (50 mL) and ether (50 mL)
10. customThe two layers were separated
11. extractionthe aqueous layer was extracted with ether (3×50 mL)
12. washThe combined organic layers were washed with brine
13. dry with materialdried (K2CO3)
14. filtrationfiltered
15. concentrationconcentrated in vacuo

ORD record

ord-1d083a69be0442f19b0476258413532e

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08796278B2