Ethyl Acetate → Tert-butyl 4-(2-ethoxy-2-oxoethyl)-4-hydroxypiperidine-1-carboxylate
Reaction equation
[Li+].CC([N-]C(C)C)C.[C:9]([O:12][CH2:13][CH3:14])(=[O:11])[CH3:10].[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][C:25](=[O:28])[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16].[Cl-].[NH4+]>C1COCC1>[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][C:25]([CH2:10][C:9]([O:12][CH2:13][CH3:14])=[O:11])([OH:28])[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:16])[CH3:17]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- -78 °C
Procedure
3.01 ml (6.02 mmol) of a 2M solution of LDA in THF are diluted in 7 ml of THF and cooled to −78° C. 540 μl (5.52 mmol) of ethyl acetate are added and the solution is stirred at −78° C. for 30 min. A solution of 1.00 g (5.01 mmol) of N-tert-butoxycarbonylpiperidin-4-one in 10 ml of THF is added dropwise. The mixture is stirred at −78° C. for a further 1 h and then warmed slowly to RT overnight. A saturated ammonium chloride solution is added and the product is extracted with dichloromethane. The removal of the solvent gives the ethyl (N-tert-butoxycarbonyl-4-hydroxypiperidin-4-yl)acetate. This crude product is chromatographed by HPLC (method 6), whereby the tert-butoxycarbonyl protecting group is cleaved by the hydrochloric acid in the eluent. 478 mg (42% of theory) of the title compound are obtained.
Workup
- stirringThe mixture is stirred at −78° C. for a further 1 h
- temperaturewarmed slowly to RT overnight
- extractionthe product is extracted with dichloromethane
- customThe removal of the solvent
Sources & evidence
- ORD record
- ord-21995f7a1cb94554a8c1ac064950b5ce
- Source dataset
- uspto-grants-2011_07
- Patent number
- US07977349B2
Reaction notes
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