Diethyl Malonate → Diethyl {[1-(tert-butoxycarbonyl)piperidin-4-yl]methyl}propanedioate

HRID 963334Notes

Reaction equation

HRID 963334 reaction equation
[C:1]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].[O-]CC.[Na+].[C:16]([O:20][C:21]([N:23]1[CH2:28][CH2:27][CH:26]([CH2:29]OS(C2C=CC(C)=CC=2)(=O)=O)[CH2:25][CH2:24]1)=[O:22])([CH3:19])([CH3:18])[CH3:17]>C(O)C>[C:16]([O:20][C:21]([N:23]1[CH2:28][CH2:27][CH:26]([CH2:29][CH:2]([C:3]([O:5][CH2:6][CH3:7])=[O:4])[C:1]([O:9][CH2:10][CH3:11])=[O:8])[CH2:25][CH2:24]1)=[O:22])([CH3:19])([CH3:17])[CH3:18]

Participants

5

Reactant 3

HCID 7761Diethyl MalonateHCID 2723922Sodium ethoxideHCID 106428511-(tert-Butoxycarbonyl)-4-((p-toluenesulfonyloxy)methyl)piperidine

Product 1

HCID 21180611Diethyl {[1-(tert-butoxycarbonyl)piperidin-4-yl]methyl}propanedioateYield 69.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Diethyl malonate (10.4 g, 65 mmol) was added to a solution of sodium ethoxide (4.42 g, 65 mmol) in ethanol (75 mL). 1-(tert-Butoxycarbonyl)-4-[(p-toluenesulfonyloxy)methyl]piperidine (25 g, 68 mmol), prepared as in Example 1, Step (a), was added and the mixture was heated at reflux for 4 hours. The mixture was cooled and partitioned between ethyl acetate and water. The ethyl acetate layer was separated, washed with water and then brine, dried over sodium sulfate, and evaporated. Purification of the residue by silica gel chromatography (25% ethyl acetate-hexane) gave 1-(tert-butoxycarbonyl)-4-[2,2-di(ethoxycarbonyl)ethyl]piperidine (16 g, 45 mmol) as an oil.

Workup

  1. additionwas added
  2. temperaturethe mixture was heated
  3. temperatureat reflux for 4 hours
  4. temperatureThe mixture was cooled
  5. custompartitioned between ethyl acetate and water
  6. customThe ethyl acetate layer was separated
  7. washwashed with water
  8. dry with materialbrine, dried over sodium sulfate
  9. customevaporated
  10. customPurification of the residue by silica gel chromatography (25% ethyl acetate-hexane)

Sources & evidence

ORD record
ord-39614943a1ae40fba3f8a2112ed14389
Source dataset
uspto-grants-1998_06
Patent number
US05763458

Reaction notes

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