Methyl iodide → Tert-butyl 4-methyl-4-(methylthio)piperidine-1-carboxylate

HRID 524912Notes

Reaction equation

HRID 524912 reaction equation
[CH3:1][C:2]1([SH:15])[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.[Li+].[CH3:17][Si]([N-][Si](C)(C)C)(C)C.CI>C1COCC1>[CH3:1][C:2]1([S:15][CH3:17])[CH2:3][CH2:4][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:6][CH2:7]1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 2733832Lithium HexamethyldisilazideHCID 71629631tert-Butyl 4-mercapto-4-methylpiperidine-1-carboxylate

Product 1

HCID 86720965Tert-butyl 4-methyl-4-(methylthio)piperidine-1-carboxylateYield 96.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of tert-butyl 4-methyl-4-sulfanyl-piperidine-1-carboxylate (380 mg, 1.642 mmol) in THF (5 mL) cooled to −78° C. was added LiHMDS (1.724 mL of 1 M, 1.724 mmol) and the solution stirred for 10 mins before MeI (256.3 mg, 0.1124 mL, 1.806 mmol) was added and the solution allowed to warm to 0° C. over approximately 1 h. The reaction was then quenched carefully by the addition of saturated ammonium chloride and extracted into EtOAc. The aqueous was further extracted with EtOAc and the combined organics were washed with brine, dried (MgSO4) and concentrated to give a yellow oil (390 mg, 96%).

Workup

  1. additionwas added
  2. customThe reaction was then quenched carefully by the addition of saturated ammonium chloride
  3. extractionextracted into EtOAc
  4. extractionThe aqueous was further extracted with EtOAc
  5. washthe combined organics were washed with brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-459917c0919c488ea286fe7c65a8439b
Source dataset
uspto-grants-2016_05
Patent number
US09340546B2

Reaction notes

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