Hydrochloric Acid → Tert-butyl 4-hydroxy-4-isobutyl-2-methylpiperidine-1-carboxylate
Reaction equation
[CH2:1]([Mg]Cl)[CH:2]([CH3:4])[CH3:3].[CH3:7][CH:8]1[CH2:13][C:12](=[O:14])[CH2:11][CH2:10][N:9]1[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16].Cl>C1COCC1>[OH:14][C:12]1([CH2:1][CH:2]([CH3:4])[CH3:3])[CH2:11][CH2:10][N:9]([C:15]([O:17][C:18]([CH3:20])([CH3:19])[CH3:21])=[O:16])[CH:8]([CH3:7])[CH2:13]1Participants
Conditions
- Temperature
- 0 °C
Procedure
Under an argon atmosphere, in a 50-mL pear-shaped evaporating flask was weighed a solution of lanthanum chloride lithium chloride complex in THF (15.6 mL) and cooled to 0° C. To the solution was added dropwise a solution of isobutylmagnesium chloride in THF (3.5 mL) and stirred at 0° C. for 3 hours. A solution of tert-butyl 2-methyl-4-oxopiperidine-1-carboxylate (1 g) in THF (2.0 mL) was further added dropwise. The reaction solution was stirred at 0° C. for 1 hour, heated to 25° C., poured to hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with water and a saturated sodium chloride solution and dried over anhydrous magnesium sulphate. The filtrate was concentrated and the resulting residue was purified by silica gel chromatography (hexane:ethyl acetate=9:1→3:1) to give the titled compound (450 mg) having the following physical properties.
Workup
- customUnder an argon atmosphere, in a 50-mL pear-shaped evaporating flask was weighed
- stirringThe reaction solution was stirred at 0° C. for 1 hour
- temperatureheated to 25° C.
- extractionextracted with ethyl acetate
- washThe organic layer was washed with water
- dry with materiala saturated sodium chloride solution and dried over anhydrous magnesium sulphate
- concentrationThe filtrate was concentrated
- customthe resulting residue was purified by silica gel chromatography (hexane:ethyl acetate=9:1→3:1)
Sources & evidence
- ORD record
- ord-c3c6677e1bbf48e4856db610b51a8e6b
- Source dataset
- uspto-grants-2016_05
- Patent number
- US09340499B2
Reaction notes
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