Reaction #303245

Reaction equation

1-Chloromethoxy-2-methoxy-ethane

1-tert-butyl 4-ethyl piperidine-1,4-dicarboxylate

LDA

→

title compound

Yield 67.0%

1-tert-butyl 4-ethyl 4-((2-methoxyethoxy)methyl)piperidine-1,4-dicarboxylate

Yield 67.0%

Solvents

THF

Conditions

Workup

1. 1
   Temperaturemaintaining the temperature below −75° C
2. 2
   Temperaturewhile maintaining the temperature below −75° C
3. 3
   workup.STIRRINGThe mixture was stirred at −78° C. for 3 hours
4. 4
   Temperatureto warm slowly to room temperature overnight
5. 5
   OtherThe mixture was quenched with sat. aq. NH4Cl
6. 6
   Extractionextracted 3 times with EtOAc
7. 7
   Washwashed with brine
8. 8
   Dryingdried over MgSO4
9. 9
   Concentrationconcentrated

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.

Source