Water → 3-Carbomethoxy-1,3-dibenzyl-4-piperidone

HRID 1042320Notes

Reaction equation

HRID 1042320 reaction equation
Cl.[CH3:2][O:3][C:4]([CH:6]1[C:11](=[O:12])[CH2:10][CH2:9][N:8]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:7]1)=[O:5].[H-].[Na+].[CH2:22](Br)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.O>CN(C=O)C.C(OCC)(=O)C>[CH3:2][O:3][C:4]([C:6]1([CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:11](=[O:12])[CH2:10][CH2:9][N:8]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:7]1)=[O:5]

Participants

7

Reactant 4

HCID 962WaterHCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 107479Methyl 1-benzyl-4-oxopiperidine-3-carboxylate hydrochloride

Product 1

HCID 542328573-Carbomethoxy-1,3-dibenzyl-4-piperidoneYield 114.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

1-Benzyl-4-oxo-piperidine-3-carboxylic acid methyl ester hydrochloride salt (1, Z=benzyl) (15 g, 52.9 mmol) was suspended in DMF (150 mL) and cooled to 0° C. Sodium hydride (4.23 g, 105.8 mmol) was added portionwise over 1 h and the contents were allowed to warm to ambient temperature and stir for a further 1 h. Benzyl bromide (6.3 mL, 53.0 mmol) was added over 15 min and the contents were stirred for a further 68 h at ambient temperature. 10 mL of water were added and the contents were diluted with 400 mL of ethyl acetate, washed with water (200 mL), saturated sodium bicarbonate (200 mL) and brine (200 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated to give 20.5 g yellow oil that was purified by flash column chromatography (3:2 cyclohexane/CH2Cl2 to 100% CH2Cl2) to give 17.52 g (98%) of the title compound as a colorless oil. LC-MS: RT=2.80 min. (M+H)+ 338, (M-OMe)+ 306.

Workup

  1. temperatureto warm to ambient temperature
  2. stirringthe contents were stirred for a further 68 h at ambient temperature
  3. washwashed with water (200 mL), saturated sodium bicarbonate (200 mL) and brine (200 mL)
  4. dry with materialThe organic layer was dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-e2878feaee4243c88932cadb1b334a92
Source dataset
uspto-grants-2013_10
Patent number
US08557839B2

Reaction notes

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