Hydrochloric Acid → HCID 59527827, compound

Temperature

-10 °C

A flame dried 500 mL four-necked round bottom flask with a mechanic stirrer was charged under inert condition with 4 mL (28 mmol) of diisopropylamine and 65 mL THF. At −5° C. 17.7 mL (28 mmol) 1.6 N butyllithium/hexane-solution was added drop wise over a period of 20 min. The light yellow solution was stirred for 30 min at −5°/−10° C. and afterwards cooled to −75° C. A solution of 7.3 g (26 mmol) piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-(2-methyl-allyl) ester in 25 mL THF was added drop wise during 20 min and stirred for 45 min at −75° C. Addition of a solution of 3.6 mL (28 mmol) TMSCl in 10 mL THF during 15 min was followed by stirring for 30 min at −75° C. and warming up over 45 minutes to ambient temperature. The colorless solution was heated for 67 h at reflux. The light yellow reaction solution was cooled to 5° C., dropwise 50 mL 2 N aq. HCl was added, stirred for 10 min and 100 mL water and 100 mL ethyl acetate was added. The aqueous layer was separated and extracted once with 150 mL ethyl acetate. The organic layers were washed twice with 200 mL brine, dried over Na2SO4, filtered and concentrated under vacuum. The residue was purified on silica eluting with a gradient formed from heptane, ethyl acetate and acetic acid to yield after evaporation of the product containing fractions 4.2 g (57%) of the title compound as off-white solid. MS ISP (m/e): 282.5 [(M+H)+].

1. customA flame dried 500 mL four-necked round bottom flask with a mechanic stirrer
2. customAt −5° C
3. temperatureafterwards cooled to −75° C
4. stirringstirred for 45 min at −75° C
5. stirringby stirring for 30 min at −75° C.
6. temperaturewarming up over 45 minutes to ambient temperature
7. temperatureThe colorless solution was heated for 67 h
8. temperatureat reflux
9. temperatureThe light yellow reaction solution was cooled to 5° C.
10. stirringstirred for 10 min
11. customThe aqueous layer was separated
12. extractionextracted once with 150 mL ethyl acetate
13. washThe organic layers were washed twice with 200 mL brine
14. dry with materialdried over Na2SO4
15. filtrationfiltered
16. concentrationconcentrated under vacuum
17. customThe residue was purified on silica eluting with a gradient
18. customformed from heptane, ethyl acetate and acetic acid
19. customto yield
20. customafter evaporation of the product
21. additioncontaining fractions 4.2 g (57%) of the title compound as off-white solid

ORD record

ord-45ce6bb4f1904d499873f232b1f8d5e5

Source dataset

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08324250B2