反应详情

To a dry, 2 L 2-neck, round-bottom flask equipped with a magnetic stirrer, a condenser, and a large 10° C. water bath was added 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (125 g, 628 mmol) and anhydrous tetrahydrofuran (1 L). To the resulting yellow solution was added methyl iodide (85 mL, 1365 mmol). Sodium t-butoxide (150 g, 1560 mmol) was then added portionwise over 30 minutes. An exotherm was detected, especially at the beginning of the addition. The reaction mixture did warm to a gentle reflux, the rate was controlled by the speed of addition of base. The mixture was stirred an additional 30 minutes. The solvent was removed in vacuo. The oily residue was treated with NH4Cl/water (500 mL), and extracted with ether (3×200 mL). The combined organics were washed with brine, dried over Na2SO4, and filtered through a short plug of silica gel. The solvent was removed in vacuo, and the resulting yellow oil had started to crystallize. It was left under high vacuum overnight. The mixture was slurried in hexane (50-100 mL) and sonicated for one minute. The yellow solid was collected by filtration and washed with hexane (100 mL). The first crop of 3,3-dimethyl-4-oxo-piperidine-1-carboxylic acid tert-butyl ester yielded a yellow solid. (See, preparation of (37) in Vice, S. et al., J. Org. Chem., 66:2487-2492 (2001).)

1. customTo a dry, 2 L 2-neck, round-bottom flask equipped with a magnetic stirrer, a condenser
2. additionAn exotherm was detected, especially at the beginning of the addition
3. temperatureThe reaction mixture did warm to a gentle reflux
4. additionthe rate was controlled by the speed of addition of base
5. customThe solvent was removed in vacuo
6. additionThe oily residue was treated with NH4Cl/water (500 mL)
7. extractionextracted with ether (3×200 mL)
8. washThe combined organics were washed with brine
9. dry with materialdried over Na2SO4
10. filtrationfiltered through a short plug of silica gel
11. customThe solvent was removed in vacuo
12. customto crystallize
13. waitIt was left under high vacuum overnight
14. customsonicated for one minute
15. filtrationThe yellow solid was collected by filtration
16. washwashed with hexane (100 mL)