Methyl iodide → 1-tert-Butyl 4-ethyl 4-methylpiperidine-1,4-dicarboxylate

HRID 2354051Notes

Reaction equation

HRID 2354051 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[CH2:11]([O:13][C:14]([CH:16]1[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]1)=[O:15])[CH3:12].[CH3:29]I>C1COCC1>[CH2:11]([O:13][C:14]([C:16]1([CH3:29])[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:27])([CH3:26])[CH3:28])=[O:23])[CH2:18][CH2:17]1)=[O:15])[CH3:12]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 27588121-Tert-butyl 4-ethyl piperidine-1,4-dicarboxylate

Product 1

HCID 162182761-tert-Butyl 4-ethyl 4-methylpiperidine-1,4-dicarboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of NaHMDS (2M in THF, 148 mmol, 74 mL, diluted to 100 mL) is cooled at −78° C. and a solution of piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester (25.74 g, 100 mmol) in THF (50 mL of solution) is added slowly. The mixture is stirred for 2 h at −78° C. Methyliodide (7.5 mL, 120 mmol) is dissolved in THF (60 mL) and the cold solution of enolate is added. The mixture is stirred at r.t. for 1 h and quenched with HCl (1M, 75 mL) and ether (200 mL). the phases are separated and the organic phase washed with HCl (1M, 2×50 mL) and NaOH (1M, 2×50 mL). The organic phase is dried (Na2SO4), filtered and evaporated to provide the crude title compound.

Workup

  1. stirringThe mixture is stirred at r.t. for 1 h
  2. customquenched with HCl (1M, 75 mL) and ether (200 mL)
  3. customthe phases are separated
  4. washthe organic phase washed with HCl (1M, 2×50 mL) and NaOH (1M, 2×50 mL)
  5. dry with materialThe organic phase is dried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated

Sources & evidence

ORD record
ord-2e354fe5a8ed465b833a480dee018345
Source dataset
uspto-grants-2010_07
Patent number
US07750161B2

Reaction notes

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