Methyl iodide → 1-Benzyl-3,3-dimethylpiperidin-4-one

HRID 1480528Notes

Reaction equation

HRID 1480528 reaction equation
[CH2:1]([N:8]1[CH2:13]CC(=O)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].I[CH3:18].[O:19]1[CH2:23][CH2:22][CH2:21]C1>>[CH2:1]([N:8]1[CH2:9][CH2:10][C:23](=[O:19])[C:22]([CH3:21])([CH3:18])[CH2:13]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 4

HCID 6328Methyl iodideHCID 8028TetrahydrofuranHCID 192201-Benzyl-4-piperidoneHCID 24758Sodium hydride

Product 1

HCID 97944131-Benzyl-3,3-dimethylpiperidin-4-one

Conditions

Temperature
60 °C

Procedure

1-Benzylpiperid-4-one (9.45 g, 8.92 mL, 49.98 mmol, 1.0 eq) was added to a suspension of sodium hydride (3.50 g of a 60% suspension in oil, 87.50 mmol, 1.75 eq) in tetrahydrofuran (100 mL). Iodomethane (9.84 g, 3.93 mL, 62.96 mmol, 1.26 eq) was added and the reaction heated to 60° C. for 5 hours. The reaction was filtered and the filtrate concentrated. The residue was partitioned between EtOAc (150 mL) and water (150 mL). The aqueous phase was extracted with EtOAc (150 mL). The organics were combined, washed with brine (150 mL), dried (Na2SO4), and concentrated under reduced pressure. Column chromatography (silica, 20→60% EtOAc-hexane) yielded the title compound as a colourless oil; 1H nmr (CDCl3) δ 7.36-7.26 (5H, m, C6H5), 3.56 (2H, s, CH2C6H5), 2.72 (2H, t, J 6.0 Hz, pipH-5 or H-6), 2.51 (2H, t, J 6.0 Hz, pipH-5 or H-6), 2.41 (2H, s, pipH-2), 1.13 (6H, s, 2×CH3); and 1-benzyl-3-methylpiperidin-4-one (3.12 g) as a colourless oil.

Workup

  1. filtrationThe reaction was filtered
  2. concentrationthe filtrate concentrated
  3. customThe residue was partitioned between EtOAc (150 mL) and water (150 mL)
  4. extractionThe aqueous phase was extracted with EtOAc (150 mL)
  5. washwashed with brine (150 mL)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-e938d8304ec14ae5b510d8ca9b4ade62
Source dataset
uspto-grants-2016_08
Patent number
US09409884B2

Reaction notes

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