Ethyl isobutyrate → 1-phenylmethyl-alpha,alpha-dimethyl-4-hydroxy-4-piperidine-acetic Acid Ethyl Ester
Reaction equation
[Li+].CC([N-]C(C)C)C.[CH2:9]([O:11][C:12](=[O:16])[CH:13]([CH3:15])[CH3:14])[CH3:10].[CH2:17]([N:24]1[CH2:29][CH2:28][C:27](=[O:30])[CH2:26][CH2:25]1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[NH4+].[Cl-]>O1CCCC1>[CH2:9]([O:11][C:12](=[O:16])[C:13]([C:27]1([OH:30])[CH2:28][CH2:29][N:24]([CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH2:25][CH2:26]1)([CH3:15])[CH3:14])[CH3:10]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- -50 °C
Procedure
Step A To a tetrahydrofuran solution (Aldrich, 1.8 M) of LDA (60 mL, 109 mmol) at −50° C. was added isobutyric acid ethyl ester (Alfa) (12.2 mL, 91 mmol) dropwise. The reaction mixture was stirred −50° C. for 1 h, then a tetrahydrofuran solution (10 mL) of 1-benzyl-piperidin-4-one (12 mL, 68 mmol) was added dropwise. The reaction mixture was warmed up to room temperature and stirred for 18 h. Aqueous saturated NH4Cl was added to quench the reaction. The mixture was extracted with ethyl ether. The organic layer was separated, and the aqueous layer was extracted with ethyl ether. The organic layers were combined, washed with brine, water, dried over MgSO4, and concentrated to give 2-(1-benzyl-4-hydroxy-piperidin-4-yl)-2-methyl-propionic acid ethyl ester as an orange oil (18.5 g, 89%).
Workup
- temperatureThe reaction mixture was warmed up to room temperature
- stirringstirred for 18 h
- customto quench
- customthe reaction
- extractionThe mixture was extracted with ethyl ether
- customThe organic layer was separated
- extractionthe aqueous layer was extracted with ethyl ether
- washwashed with brine, water
- dry with materialdried over MgSO4
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-ad311c1733d64653953c2a78ea26c9d6
- Source dataset
- uspto-grants-2013_01
- Patent number
- US08354444B2
Reaction notes
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