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

HRID 400431

Reaction equation

HRID 400431 reaction equation
[CH:1](NC(C)C)(C)C.[CH3:8][O:9][C:10]([CH:12]1[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]1)=[O:11].CI>C1COCC1>[CH3:8][O:9][C:10]([C:12]1([CH3:1])[CH2:13][CH2:14][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:16][CH2:17]1)=[O:11]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 7912DiisopropylamineHCID 3928701-N-Boc-4-Piperidinecarboxylic acid methyl ester

Product 1

HCID 463183881-tert-Butyl 4-methyl 4-methylpiperidine-1,4-dicarboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

137 mL Diisopropylamine in 3390 mL THF was cooled to 0° C. and 360 mL n-buthyllithium was added dropwise under nitrogen. The reaction was cooled to −78° C. and a solution of 180 mL piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-methyl ester in 1800 mL THF was added dropwise over 1 h. The reaction was stirred at −78° C. for 2 h and then 168 mL methyliodide in 300 mL THF was added in one portion. The mixture was stirred 2 h at −78° C. and then allowed to warm to RT. The reaction was quenched with saturated aqueous sodium sulfate solution, the organig phase was separated, dried and evaporated. The residue was purified by chromatography on silica gel to give 155 g of the desired product.

Workup

  1. addition360 mL n-buthyllithium was added dropwise under nitrogen
  2. stirringThe mixture was stirred 2 h at −78° C.
  3. temperatureto warm to RT
  4. customThe reaction was quenched with saturated aqueous sodium sulfate solution
  5. customthe organig phase was separated
  6. customdried
  7. customevaporated
  8. customThe residue was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-bb0709d09d8642869019a120a35b85a9
Source dataset
uspto-grants-2014_06
Patent number
US08741892B2

Linked notes

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