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

Temperature

0 °C

To a solution of piperidine-1,3-dicarboxylic acid 3-((Z)-but-2-enyl)ester 1-tert-butyl ester (68.3 g) in tetrahydrofuran (700 ml) cooled to −74° C. was added lithium hexamethyl disilazide (1.6M tetrahydrofuran solution, 166 ml). The reaction mixture was warmed to 0° C. over 35 minutes, stirred at the same temperature for additional 25 minutes, and cooled to −74° C. again. To the mixture was added trimethylsilyl chloride (39.6 ml). The reaction mixture was warmed to room temperature over 70 minutes, and stirred at the same temperature for additional 4 hours. To the mixture were sequentially added water (600 ml), 2M aqueous sodium hydroxide solution (70 ml), and the mixture was washed with n-hexane (600 ml). The separated aqueous layer was acidified by 2M aqueous hydrochloric acid solution, followed by extracted with ethyl acetate (300 ml, 200 ml, 150 ml) three times. The combined organic layer was washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was slurry-washed with n-hexane/ethyl acetate solution (10/1) to give the titled compound (42.5 g).

1. temperaturecooled to −74° C. again
2. temperatureThe reaction mixture was warmed to room temperature over 70 minutes
3. stirringstirred at the same temperature for additional 4 hours
4. washthe mixture was washed with n-hexane (600 ml)
5. extractionby extracted with ethyl acetate (300 ml, 200 ml, 150 ml) three times
6. washThe combined organic layer was washed with saturated aqueous sodium chloride solution
7. dry with materialdried over anhydrous sodium sulfate
8. concentrationconcentrated under reduced pressure
9. washThe resulting residue was slurry-washed with n-hexane/ethyl acetate solution (10/1)

ORD record

ord-f9103c4705a0465a8c9247f29aa44915

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08609647B2