1-(Chloromethoxy)-2-methoxyethane → 1-Tert-butyl 4-ethyl 4-((2-methoxyethoxy)methyl)piperidine-1,4-dicarboxylate
Reaction equation
[N:1]1([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:6][CH2:5][CH:4]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH2:3][CH2:2]1.[Li+].CC([N-]C(C)C)C.Cl[CH2:28][O:29][CH2:30][CH2:31][O:32][CH3:33]>C1COCC1>[CH3:28][O:29][CH2:30][CH2:31][O:32][CH2:33][C:4]1([C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH2:3][CH2:2][N:1]([C:12]([O:14][C:15]([CH3:17])([CH3:16])[CH3:18])=[O:13])[CH2:6][CH2:5]1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- -78 °C
Procedure
To a solution of 1-tert-butyl 4-ethyl piperidine-1,4-dicarboxylate (2.0 g, 7.8 mmol) in THF (70 mL) at −78° C. was added dropwise LDA over 8 minutes, maintaining the temperature below −75° C. The mixture was stirred at −78° C. for 1 hour. 1-Chloromethoxy-2-methoxy-ethane (0.97 g. 7.8 mmol) was added dropwise while maintaining the temperature below −75° C. The mixture was stirred at −78° C. for 3 hours, and then allowed to warm slowly to room temperature overnight. The mixture was quenched with sat. aq. NH4Cl and extracted 3 times with EtOAc. The organics were combined, washed with brine, dried over MgSO4, and concentrated. Silica gel chromatography (10-20% ethyl acetate:hexanes) gave the title compound in 67% yield. MS (ES+) [M+H]+=346.
Workup
- temperaturemaintaining the temperature below −75° C
- temperaturewhile maintaining the temperature below −75° C
- stirringThe mixture was stirred at −78° C. for 3 hours
- temperatureto warm slowly to room temperature overnight
- customThe mixture was quenched with sat. aq. NH4Cl
- extractionextracted 3 times with EtOAc
- washwashed with brine
- dry with materialdried over MgSO4
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-e4445a29e7334c2c9615d8c29e353459
- Source dataset
- uspto-grants-2012_06
- Patent number
- US08193202B2
Reaction notes
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