Diethyl Malonate → 5-(1-Benzyloxycarbonyl-4-piperidyl)-2-carboxyvaleric acid

HRID 649397Notes

Reaction equation

HRID 649397 reaction equation
[Na].[C:2]([O:10]CC)(=[O:9])[CH2:3][C:4]([O:6]CC)=[O:5].C1(C)C=CC(S(O[CH2:23][CH2:24][CH2:25][CH:26]2[CH2:31][CH2:30][N:29]([C:32]([O:34][CH2:35][C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)=[O:33])[CH2:28][CH2:27]2)(=O)=O)=CC=1.[OH-].[Na+]>C(O)C.O>[CH2:35]([O:34][C:32]([N:29]1[CH2:30][CH2:31][CH:26]([CH2:25][CH2:24][CH2:23][CH:3]([C:4]([OH:6])=[O:5])[C:2]([OH:10])=[O:9])[CH2:27][CH2:28]1)=[O:33])[C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1

Participants

7

Reactant 4

HCID 7761Diethyl MalonateHCID 14798Sodium HydroxideHCID 5360545SodiumHCID 136527313-(1-Benzyloxycarbonyl-4-piperidyl)propyl p-toluenesulfonate

Product 1

HCID 201436805-(1-Benzyloxycarbonyl-4-piperidyl)-2-carboxyvaleric acid

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 962WaterSolvent3×

Procedure

In 300 ml of ethanol is dissolved 5.8 g of sodium, and 40 g of diethyl malonate is added to the solution, followed by stirring. 3-(1-Benzyloxycarbonyl-4-piperidyl)propyl p-toluenesulfonate (90.5 g) is added to this mixture followed by refluxing with stirring for 2 hours. After cooling, 1 l of water is added to the reaction solution, which is then extracted with 500 ml of ethyl acetate. The extract is dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give ethyl 5-(1-benzyloxycarbonyl-4-piperidyl)-2-ethoxycarbonylvalearate as an oily material. This product is dissolved in 200 ml of ethanol, and a solution of 34 g of sodium hydroxide in 200 ml of water is added dropwise to the solution with stirring. After the addition is completed, 300 ml of water is added to the reaction solution, which is then extracted with a mixture of ether and petroleum ether (1:1, 300 ml). The aqueous layer is made acidic with conc. hydrochloric acid, followed by extraction with 500 ml of ethyl acetate. The extract is washed with water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give 5-(1-benzyloxycarbonyl-4-piperidyl)-2-carboxyvaleric acid as an oily material. This product is heated at 160° to 170° C. with stirring for 45 minutes to give 50 g of 5-(1-benzyloxycarbonyl-4-piperidyl)valeric acid as an oily material.

Workup

  1. additionis added to the solution
  2. temperatureby refluxing
  3. stirringwith stirring for 2 hours
  4. temperatureAfter cooling
  5. extractionis then extracted with 500 ml of ethyl acetate
  6. dry with materialThe extract is dried over anhydrous magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customto give ethyl 5-(1-benzyloxycarbonyl-4-piperidyl)-2-ethoxycarbonylvalearate as an oily material
  9. stirringwith stirring
  10. additionAfter the addition
  11. extractionis then extracted with a mixture of ether and petroleum ether (1:1, 300 ml)
  12. extractionfollowed by extraction with 500 ml of ethyl acetate
  13. washThe extract is washed with water
  14. dry with materialdried over anhydrous magnesium sulfate
  15. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-b48cc7112aa649f8b7e46e5602a2a926
Source dataset
uspto-grants-1988_04
Patent number
US04739066

Reaction notes

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