Methyl iodide → 1-tert-Butyl 3-ethyl 3-methylpiperidine-1,3-dicarboxylate

HRID 412239Notes

Reaction equation

HRID 412239 reaction equation
[CH:1]([N-]C(C)C)(C)C.[Li+].[N:9]1([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:14][CH2:13][CH2:12][CH:11]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:10]1.CI>C1COCC1>[CH3:1][C:11]1([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:12][CH2:13][CH2:14][N:9]([C:20]([O:22][C:23]([CH3:25])([CH3:24])[CH3:26])=[O:21])[CH2:10]1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 3577271-Tert-butyl 3-ethyl piperidine-1,3-dicarboxylateHCID 2724682Lithium diisopropylamide

Product 1

HCID 205853941-tert-Butyl 3-ethyl 3-methylpiperidine-1,3-dicarboxylateYield 72.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-50 °C

Procedure

To a cold (−78° C.) solution of lithium diisopropylamide (LDA) (23.3 mmol) in THF (10 mL) under an argon atmosphere was added dropwise a solution of 1-tert-butyl 3-ethyl 1,3-piperidinedicarboxylate (3.0 g, 11.6 mmol) in THF (5 mL), then stirred at −50° C. for 2 hrs. To the resulting mixture was added a solution of MeI (1.98 g, 14 mmol) in THF at −50° C. The reaction mixture was allowed to warm to room temperature, and quenched with saturated aqueous NH4Cl solution. The mixture was concentrated under reduced pressure, and the residue was partitioned between ethyl acetate and water. The organic phase was separated, dried over MgSO4, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (hexane:ethyl acetate, 9:1) to give 1-tert-butyl 3-ethyl 3-methyl-1,3-piperidinedicarboxylate as a pale yellow oil (2.27 g, yield; 72%).

Workup

  1. temperatureto warm to room temperature
  2. customquenched with saturated aqueous NH4Cl solution
  3. concentrationThe mixture was concentrated under reduced pressure
  4. customthe residue was partitioned between ethyl acetate and water
  5. customThe organic phase was separated
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude product was purified by column chromatography on silica gel (hexane:ethyl acetate, 9:1)

Sources & evidence

ORD record
ord-cdf64c3a831b4390a9641f3af207e168
Source dataset
uspto-grants-2003_05
Patent number
US06562811B1

Reaction notes

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