Water → tert-Butyl 3,3-dimethyl-4-oxopiperidine-1-carboxylate

反応式

O.[C:2]([O:6][C:7]([N:9]1[CH2:14]CC(=O)[CH2:11][CH2:10]1)=[O:8])([CH3:5])([CH3:4])[CH3:3].CI.[CH3:18]C(C)([O-])C.[Na+].[O:24]1[CH2:28][CH2:27][CH2:26]C1>>[C:2]([O:6][C:7]([N:9]1[CH2:10][CH2:11][C:28](=[O:24])[C:27]([CH3:26])([CH3:18])[CH2:14]1)=[O:8])([CH3:5])([CH3:4])[CH3:3]

参加物

反応物 5

HCID 962Water

HCID 6328Methyl iodide

HCID 8028Tetrahydrofuran

HCID 735900tert-Butyl 4-oxopiperidine-1-carboxylate

HCID 23676156Sodium t-butoxide

生成物 1

HCID 22278899tert-Butyl 3,3-dimethyl-4-oxopiperidine-1-carboxylate

実験手順

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).)