Dimethylformamide → tert-butyl N-methyl-N-(piperidin-3-yl)carbamate

HRID 2112890Notes

Reaction equation

HRID 2112890 reaction equation
[H-].[Na+].C(OC([N:13]1[CH2:18][CH2:17][CH2:16][CH:15]([NH:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:14]1)=O)C1C=CC=CC=1.CI.[CH3:29]N(C)C=O>[Pd].C(O)C>[C:23]([O:22][C:20](=[O:21])[N:19]([CH3:29])[CH:15]1[CH2:16][CH2:17][CH2:18][NH:13][CH2:14]1)([CH3:24])([CH3:25])[CH3:26]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 22258937Benzyl 3-(tert-butoxycarbonylamino)piperidine-1-carboxylate2×

Product 1

HCID 22449166tert-butyl N-methyl-N-(piperidin-3-yl)carbamate

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

In a water bath at room temperature, sodium hydride (60% in oil) (0.4 g) was added to a mixture of 3-t-butoxycarbonylaminopiperidin-1-carboxylic acid benzyl ester (compound 25a) (3.3 g), methyl iodide (0.75 mL), and N,N-dimethylformamide (20 mL), and this was stirred at room temperature for four hours. The reaction solution was extracted using ethyl acetate and water, the organic layer was washed with water, and then with saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography using 10% to 20% ethyl acetate/hexane to give an oily substance (3.04 g). A mixture of all of the resulting material with ethanol (20 mL) and 10% palladium on carbon was stirred under hydrogen atmosphere at room temperature for five hours. The catalyst was filtered off, and the filtrate was concentrated to give the title compound (1.82 g).

Workup

  1. extractionThe reaction solution was extracted
  2. washthe organic layer was washed with water
  3. dry with materialwith saturated brine, dried over anhydrous magnesium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel column chromatography
  6. customto give an oily substance (3.04 g)
  7. stirringwas stirred under hydrogen atmosphere at room temperature for five hours
  8. filtrationThe catalyst was filtered off
  9. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-7df27a09b20e469a91bdbf6049b88d26
Source dataset
uspto-grants-2009_04
Patent number
US07524847B2

Reaction notes

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