Sodium → 5-(Tetrahydro-2H-pyran-4-YL)cyclohexane-1,3-dione

HRID 43314Notes

Reaction equation

HRID 43314 reaction equation
C([C:3](CC)(C([O-])=O)[C:4]([O-])=[O:5])C.[Na].[O:13]1[CH2:18][CH2:17][CH:16]([CH:19]=[CH:20][C:21](=[O:23])[CH3:22])[CH2:15][CH2:14]1>C(O)C>[O:13]1[CH2:18][CH2:17][CH:16]([CH:19]2[CH2:3][C:4](=[O:5])[CH2:22][C:21](=[O:23])[CH2:20]2)[CH2:15][CH2:14]1

Participants

5

Reactant 3

HCID 5360545SodiumHCID 69515632,2-DiethylpropanedioateHCID 571371831-(4-Tetrahydropyranyl)but-1-en-3-one

Product 1

HCID 189213635-(Tetrahydro-2H-pyran-4-YL)cyclohexane-1,3-dione

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

Diethylmalonate (8.86 ml, 58 mmol) is added dropwise over 3 minutes to a chilled (ice-bath) solution of sodium (1.48 g, 64 mmol) in ethanol (80 ml). Once the addition is complete the cooling bath is removed and reaction is stirred for 25 minutes at room temperature, then the reaction mixture is cooled again in an ice-bath. A solution of 4-(tetrahydropyran-4-yl)-3-buten-2-one (7.50 g, 49 mmol) in ethanol (45 ml) is added to the reaction mixture via a dropping funnel over 15 minutes. Once the addition is complete, the cooling bath is removed and the yellow solution is stirred at room temperature for 19 hours. The reaction mixture is acidified to pH 3 by dropwise addition of 2M aqueous hydrochloric acid, water added to dissolve the precipitate and the reaction mixture is extracted into dichloromethane. The organic extracts are dried over anhydrous magnesium sulphate, filtered and the filtrate concentrated in vacuo. The residue is taken up in isopropanol (50 ml) and a 2M aqueous solution of sodium hydroxide (140 ml) added. The reaction mixture is stirred at room temperature for 20 hours. The reaction mixture is concentrated in vacuo to remove isopropanol, then heated to 70° C. A solution of 2M aqueous hydrochloric acid is added carefully until the reaction mixture reaches pH 2. The reaction mixture is heated for 2½ hours at 75° C., then cooled to room temperature and the product is extracted into ethyl acetate. The organic extracts are combined, dried over anhydrous magnesium sulphate, filtered and the filtrate concentrated in vacuo to give 5-(tetrahydropyran-4-yl)cyclohexane-1,3-dione.

Workup

  1. additionOnce the addition
  2. customis removed
  3. customreaction
  4. temperaturethe reaction mixture is cooled again in an ice-bath
  5. additionOnce the addition
  6. customthe cooling bath is removed
  7. stirringthe yellow solution is stirred at room temperature for 19 hours
  8. additionThe reaction mixture is acidified to pH 3 by dropwise addition of 2M aqueous hydrochloric acid, water
  9. additionadded
  10. dissolutionto dissolve the precipitate
  11. extractionthe reaction mixture is extracted into dichloromethane
  12. dry with materialThe organic extracts are dried over anhydrous magnesium sulphate
  13. filtrationfiltered
  14. concentrationthe filtrate concentrated in vacuo
  15. additiona 2M aqueous solution of sodium hydroxide (140 ml) added
  16. stirringThe reaction mixture is stirred at room temperature for 20 hours
  17. concentrationThe reaction mixture is concentrated in vacuo
  18. customto remove isopropanol
  19. temperatureheated to 70° C
  20. additionA solution of 2M aqueous hydrochloric acid is added carefully until the reaction mixture
  21. temperatureThe reaction mixture is heated for 2½ hours at 75° C.
  22. temperaturecooled to room temperature
  23. extractionthe product is extracted into ethyl acetate
  24. dry with materialdried over anhydrous magnesium sulphate
  25. filtrationfiltered
  26. concentrationthe filtrate concentrated in vacuo

Sources & evidence

ORD record
ord-3e6da8fd35424ffea4abb8169e554dc5
Source dataset
uspto-grants-2013_09
Patent number
US08536351B2

Reaction notes

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