1,1,1-Trifluoro-2-iodoethane → 4-(2,2,2-Trifluoro-ethyl)-piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester

温度

-10 °C

Under a argon atmosphere a vacuum dried 750 mL four necked flask (with mechanical stirrer) was charged with 6.6 mL diisopropylamine and 100 mL THF. The solution was cooled to −5° C./−10° C. 29.1 mL of 1.6M n-butyllithium in hexane was added 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 10 g (38.8 mmol) ethyl 1-tert-butoxycarbonylpiperidine in 75 mL THF was added over a period of 50 min. The yellow solution was stirred at −75° C. for 2 h. A solution of 9.8 g (46.7 mmol) 2,2,2-trifluoroethyl iodide in 25 mL THF was added dropwise over a period of 45 min. The reaction was stirred for 1 h at −75° C. and allowed to warm up over night to ambient temperature. The reaction was cooled down to 0° C., quenched with 250 mL 10% citric acid aq. solution The aqueous layer was separated and extracted twice with 200 mL ethyl acetate. The organic layers were washed once with 200 mL brine, dried over Na2SO4, filtered and evaporated.

1. dry with materialUnder a argon atmosphere a vacuum dried 750 mL four necked flask (with mechanical stirrer)
2. additionwas charged with 6.6 mL diisopropylamine and 100 mL THF
3. addition29.1 mL of 1.6M n-butyllithium in hexane was added over a period of 20 min
4. temperatureafterwards cooled to −75° C
5. stirringThe yellow solution was stirred at −75° C. for 2 h
6. stirringThe reaction was stirred for 1 h at −75° C.
7. temperatureto warm up over night to ambient temperature
8. temperatureThe reaction was cooled down to 0° C.
9. customquenched with 250 mL 10% citric acid aq. solution The aqueous layer
10. customwas separated
11. extractionextracted twice with 200 mL ethyl acetate
12. washThe organic layers were washed once with 200 mL brine
13. dry with materialdried over Na2SO4
14. filtrationfiltered
15. customevaporated

ORDレコード

ord-f47a936172344928aaa9b62cce57a353

出典データセット

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08324250B2