Dimethyl Carbonate → 1-tert-Butyl 3-methyl 4-oxopiperidine-1,3-dicarboxylate

HRID 2207338Notes

Reaction equation

HRID 2207338 reaction equation
[H-].[Na+].[C:3](=O)([O:6]C)[O:4][CH3:5].[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][C:19](=[O:22])[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10].[OH-].[Na+]>C1(C)C=CC=CC=1.CO.O.C(O)(=O)C>[CH3:5][O:4][C:3]([CH:20]1[C:19](=[O:22])[CH2:18][CH2:17][N:16]([C:14]([O:13][C:9]([CH3:12])([CH3:10])[CH3:11])=[O:15])[CH2:21]1)=[O:6]

Participants

9

Reactant 4

HCID 12021Dimethyl CarbonateHCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylate

Product 1

HCID 112768931-tert-Butyl 3-methyl 4-oxopiperidine-1,3-dicarboxylateYield 81%

Reagents, catalysts & solvents 4

HCID 887MethanolCatalystHCID 176Acetic AcidSolventHCID 962WaterSolventHCID 1140TolueneSolvent2×

Conditions

Temperature
80 °C

Procedure

To a suspension of 60% sodium hydride (3.5 g, 88 mMol) in dry toluene (50 mL), dimethyl carbonate (4.32 g, 48.0 mMol) was added dropwise in 0.5 h at room temperature under an atmosphere of nitrogen. After addition of a few drops of methanol, a solution of 1-tert-butoxycarbonyl-4-piperidone (4.8 g, 24 mMol) dissolved in dry toluene (20 mL) was added dropwise to the reaction mixture while stirring at 80° C. over 1 h. The reaction mixture was stirred for 3 h at the same temperature and then cooled to 0° C. (ice bath) and adjusted to pH 6-6.5 with acetic acid. The resulting cold mixture was diluted with water (10 mL) and adjusted to pH 8 with 5% sodium hydroxide solution. The toluene layer was separated and the aqueous layer was extracted with toluene (20 mL). The combined organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure The compound was dried in vacuum to give methyl-1-tert-butoxycarbonyl-4-oxo-3-piperidine carboxylate (5.0 g, 80%). The compound obtained was carried to next reaction without any further purification.

Workup

  1. additionwas added dropwise in 0.5 h at room temperature under an atmosphere of nitrogen
  2. additionwas added dropwise to the reaction mixture
  3. stirringThe reaction mixture was stirred for 3 h at the same temperature
  4. temperaturecooled to 0° C. (ice bath)
  5. customThe toluene layer was separated
  6. extractionthe aqueous layer was extracted with toluene (20 mL)
  7. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
  8. concentrationconcentrated under reduced pressure The compound
  9. customwas dried in vacuum

Sources & evidence

ORD record
ord-c26678e70895483c887b93141eb51258
Source dataset
uspto-grants-2016_06
Patent number
US09376437B2

Reaction notes

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