Chlorotrimethylsilane → 3-(1-Methylallyl)piperidine-1,3-dicarboxylic acid 1-tert-butyl ester

온도

0 °C

To a solution of piperidine-1,3-dicarboxylic acid 3-((E)-but-2-enyl)ester 1-tert-butyl ester (105.7 g) in tetrahydrofuran (1000 ml) cooled to −68° C. was added lithium hexamethyl disilazide (1.1M tetrahydrofuran solution, 411 ml). The reaction mixture was warmed to 0° C. over 20 minutes, stirred at the same temperature for additional 30 minutes, and then cooled to −68° C. again. To the mixture was added trimethylsilyl chloride (56.6 ml). The reaction mixture was warmed to room temperature over 2 hours, and stirred at the same temperature for additional 2 hours. After ice-cooling, to the mixture were sequentially added water (1000 ml) and 2M aqueous sodium hydroxide solution (136 ml), and the mixture was washed with n-hexane (1000 ml). The separated aqueous layer was acidified by 2M aqueous hydrochloric acid solution, and then extracted with ethyl acetate (800 ml). The organic layer was sequentially washed with water (700 ml) and saturated aqueous sodium chloride solution (400 ml), and the separated aqueous layer was extracted with ethyl acetate (600 ml) again. The combined organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was slurry-washed with n-hexane/ethyl acetate solution (6/1, 700 ml) to give the titled compound (59.8 g). The filtrate was concentrated under reduced pressure, and the resulting residue was slurry-washed with n-hexane/ethyl acetate solution (4/1, 200 ml) again to give a solid (14.4 g). The solid was slurry-washed with n-hexane/ethyl acetate solution (5/1, 100 ml) again to give the titled compound (11.9 g). The resultant was combined to give the titled compound (71.7 g).

1. temperaturecooled to −68° C. again
2. temperatureThe reaction mixture was warmed to room temperature over 2 hours
3. stirringstirred at the same temperature for additional 2 hours
4. temperatureAfter ice-cooling, to the mixture
5. washthe mixture was washed with n-hexane (1000 ml)
6. extractionextracted with ethyl acetate (800 ml)
7. washThe organic layer was sequentially washed with water (700 ml) and saturated aqueous sodium chloride solution (400 ml)
8. extractionthe separated aqueous layer was extracted with ethyl acetate (600 ml) again
9. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
10. concentrationconcentrated under reduced pressure
11. washThe resulting residue was slurry-washed with n-hexane/ethyl acetate solution (6/1, 700 ml)

ORD 기록

ord-faaee58d47ff445eab9e18cb8fd08bd3

출처 데이터셋

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08609647B2