Methyl iodide → tert-Butyl 3-methyl-4-oxopiperidine-1-carboxylate

HRID 2179424Notes

Reaction equation

HRID 2179424 reaction equation
[O:1]=[C:2]1[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.[CH:15]([N-]C(C)C)(C)C.[Li+].IC>O1CCCC1>[CH3:15][CH:7]1[C:2](=[O:1])[CH2:3][CH2:4][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:6]1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 2724682Lithium diisopropylamide

Product 1

HCID 22644642tert-Butyl 3-methyl-4-oxopiperidine-1-carboxylateYield 638.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl 4-oxopiperidine-1-carboxylate (10.0 g, 50.2 mmol) in tetrahydrofuran (50 mL) was added lithium diisopropylamide (2.0 M in THF, 1.5 mL, 3.01 mmol) at −78° C. After 1 h, iodomethane (0.19 mL, 3.01 mmol) was added and the reaction mixture was allowed to warm to ambient temperature over 48 h before being quenched with 1M ammonium chloride and extracted with ethyl acetate. The organic layer was concentrated in vacuo and the residue purified by flash column chromatography (SiO2, 9:1 hexanes/ethyl acetate) to give tert-butyl 3-methyl-4-oxopiperidine-1-carboxylate (4.1 g, 38%) as a yellow solid: 1H NMR (CDCl3, 300 MHz) δ 4.24-4.12 (m, 2H), 3.32-3.20 (m, 1H), 2.94-2.75 (m, 1H), 2.61-2.38 (m, 3H), 1.50 (s, 9H), 1.05 (d, J=6.9 Hz, 3H).

Workup

  1. custombefore being quenched with 1M ammonium chloride
  2. extractionextracted with ethyl acetate
  3. concentrationThe organic layer was concentrated in vacuo
  4. customthe residue purified by flash column chromatography (SiO2, 9:1 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-f6723c8f03534ef3bb66166e80a605a4
Source dataset
uspto-grants-2015_06
Patent number
US09067949B2

Reaction notes

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