Methyl iodide → tert-Butyl 4-(2-(benzyl(methyl)amino)ethyl)piperidine-1-carboxylate

HRID 1193335Notes

Reaction equation

HRID 1193335 reaction equation
[CH2:1]([NH:8][CH2:9][CH2:10][CH:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].I[CH3:27]>C1COCC1.CN(C=O)C.O>[CH2:1]([N:8]([CH3:27])[CH2:9][CH2:10][CH:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 66799249tert-Butyl 4-(2-(benzylamino)ethyl)piperidine-1-carboxylate

Product 1

HCID 19261850tert-Butyl 4-(2-(benzyl(methyl)amino)ethyl)piperidine-1-carboxylateYield 34%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

At 0° C., a solution of tert-butyl 4-(2-(benzylamino)ethyl)piperidine-1-carboxylate (400 mg, 1.25 mmol, 1 eq) in THF (10 ml) was added dropwise to a suspension of NaH (110 mg, 2.74 mmol, 1.3 eq, 60% in mineral oil) in DMF (4 ml), and stirring was carried out for 30 min. Then a solution of iodomethane (93 μl, 1.5 mmol, 1.2 eq) in THF (2 ml) was added dropwise at 0° C., and stirring was carried out for 2 h at RT. After monitoring by thin-layer chromatography, the reaction mixture was diluted with water (5 ml) and extracted with ethyl acetate (2×50 ml). The combined organic phases were washed with water and sat. NaCl solution (in each case 50 ml), dried over sodium sulfate and concentrated under reduced pressure. After purification by column chromatography (silica gel, 60% ethyl acetate in hexane), a light-yellow solid was obtained. Yield: 34% (140 mg, 0.42 mmol).

Workup

  1. stirringstirring
  2. waitwas carried out for 2 h at RT
  3. extractionextracted with ethyl acetate (2×50 ml)
  4. washThe combined organic phases were washed with water and sat. NaCl solution (in each case 50 ml),
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customAfter purification by column chromatography (silica gel, 60% ethyl acetate in hexane)
  8. customa light-yellow solid was obtained

Sources & evidence

ORD record
ord-9c5569e6a9114cfa92547c554fe8cc4c
Source dataset
uspto-grants-2014_03
Patent number
US08680159B2

Reaction notes

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