Methyl iodide → tert-Butyl 3,3-dimethyl-4-oxopiperidine-1-carboxylate

HRID 2355897Notes

Reaction equation

HRID 2355897 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13]CC(=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].I[CH3:18].[O:19]1[CH2:23][CH2:22][CH2:21]C1>>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][C:23](=[O:19])[C:22]([CH3:21])([CH3:18])[CH2:13]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 4

HCID 6328Methyl iodideHCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylate

Product 1

HCID 22278899tert-Butyl 3,3-dimethyl-4-oxopiperidine-1-carboxylate

Procedure

To a solution of 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (16 g, 80 mmol) in tetrahydrofuran (400 mL) at 0° C. was added sodium hydride (4.1 g, 2.1 equiv) in 4 portions. To this was added iodomethane (12.5 mL, 2.5 equiv) dropwise. The reaction was allowed to gradually warm to room temperature and stirred overnight. The reaction was concentrated, dissolved in diethyl ether, washed with brine, dried over magnesium sulfate, and concentrated. The product was crystallized from hot pentane (2×) to give 5.9 g (32%). 1H-NMR (CDCl3, 500 MHz) δ 1.09 (s, 6H), 1.47 (s, 9H), 2.47 (dd, J=6.4, 6.4, 2H), 3.41 (m, 2H), 3.70 (m, 2H). Mass spec.: 250.12 (M+Na)+.

Workup

  1. concentrationThe reaction was concentrated
  2. dissolutiondissolved in diethyl ether
  3. washwashed with brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated
  6. customThe product was crystallized from hot pentane (2×)
  7. customto give 5.9 g (32%)

Sources & evidence

ORD record
ord-435f0c131edc4927b2d610bcce1ffbe2
Source dataset
uspto-grants-2010_07
Patent number
US07754732B2

Reaction notes

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