Water → tert-Butyl 4-cyano-4-methylpiperidine-1-carboxylate

HRID 390325

Reaction equation

HRID 390325 reaction equation
[C:1]([CH:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1)#[N:2].[CH3:16][Si]([N-][Si](C)(C)C)(C)C.[Li+].IC.O>C1COCC1>[C:1]([C:3]1([CH3:16])[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1)#[N:2]

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 1514443Tert-butyl 4-cyanopiperidine-1-carboxylateHCID 2733832Lithium Hexamethyldisilazide

Product 1

HCID 46835621tert-Butyl 4-cyano-4-methylpiperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl 4-cyanopiperidine-1-carboxylate (0.500 g, 2.38 mmol) in 15 mL of THF at −78° C. was added lithium bis(trimethylsilyl)amide (1 M solution in diethyl ether, 5.23 mL, 5.23 mmol). After 20 min, iodomethane (0.338 g, 2.38 mmol) was added dropwise, and the reaction was slowly warmed to rt. After 15 h, the mixture was cooled to 0° C., treated with water, and extracted 3× with ethyl acetate. The solution was extracted 3× with ethyl acetate, and the combined organic solution was washed with water and brine, dried over sodium sulfate, filtered, and concentrated in vacuo to provide tert-butyl 4-cyano-4-methylpiperidine-1-carboxylate that gave a proton NMR spectra consistent with theory.

Workup

  1. waitAfter 15 h
  2. temperaturethe mixture was cooled to 0° C.
  3. extractionextracted 3× with ethyl acetate
  4. extractionThe solution was extracted 3× with ethyl acetate
  5. washthe combined organic solution was washed with water and brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-454eebe664044bada4195fc24971f482
Source dataset
uspto-grants-2013_02
Patent number
US08383638B2

Linked notes

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