Tetrahydrofuran → Sodium 4-(ethoxycarbonyl)-3-ethyl-2-(methoxycarbonyl)cyclopenta-1,3-dienolate

HRID 1969611Notes

Reaction equation

HRID 1969611 reaction equation
C1COCC1.[H-].[Na+:7].[C:8]([CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])(=O)[CH2:9][CH3:10].Cl[CH2:19][C:20](=[O:26])[CH2:21][C:22]([O:24][CH3:25])=[O:23]>O.CCOCC>[CH2:16]([O:15][C:13]([C:12]1[CH2:19][C:20]([O-:26])=[C:21]([C:22]([O:24][CH3:25])=[O:23])[C:8]=1[CH2:9][CH3:10])=[O:14])[CH3:17].[Na+:7]

Participants

7

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 24758Sodium hydrideHCID 36240Methyl 4-chloroacetoacetateHCID 78656Ethyl 3-oxovalerate

Product 1

HCID 58009817Sodium 4-(ethoxycarbonyl)-3-ethyl-2-(methoxycarbonyl)cyclopenta-1,3-dienolateYield 89%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
-10 °C

Procedure

A round bottom flask was charged with THF (1.5 L) followed by the portionwise addition of NaH (60% dispersion in mineral oil, 70.0 g, 1.75 mol). Additional THF (500 mL) was added and the resulting mixture was cooled to about −10° C. Ethyl propionylacetate (250 mL, 1.80 mol) was added dropwise over about 1 h in order to keep internal temperature below about 10° C. The resulting mixture was stirred at ambient temperature for about 0.5 h to give a clear yellow solution and then methyl 4-chloroacetoacetate (100 mL, 0.88 mol) was added dropwise over about 5 min. The resulting mixture was heated at about 50° C. for about 19 h to give a reddish orange suspension. The reaction mixture was cooled to ambient temperature, concd under reduced pressure and the resulting liquid was transferred to a beaker and diluted with water (350 mL). The mixture was stirred in an ice bath for about 2 h. The solid was collected by vacuum filtration and the filter cake was rinsed with water (150 mL) and dried under vacuum for about 1 h. The solid was suspended in Et2O (1.5 L), filtered, washed with Et2O (1.5 L), and dried under vacuum. The resulting solid was azeotroped with toluene (1 L) to give a solid that was re-suspended in Et2O (1 L) and collected by vacuum filtration. The filter cake was washed with Et2O (500 mL) and dried under vacuum to give sodium 4-(ethoxycarbonyl)-3-ethyl-2-(methoxycarbonyl)cyclopenta-1,3-dienolate (204.2 g, 89%) as beige solid: 1H NMR (DMSO-d6) δ 3.94 (q, J=7.1 Hz, 2H), 3.46 (s, 3H), 3.04 (q, J=7.2 Hz, 2H), 2.66 (s, 2H), 1.13 (t, J=7.1 Hz, 3H), 0.99 (t, J=7.3 Hz, 3H).

Workup

  1. customtemperature below about 10° C
  2. customto give a clear yellow solution
  3. temperatureThe resulting mixture was heated at about 50° C. for about 19 h
  4. customto give a reddish orange suspension
  5. temperatureThe reaction mixture was cooled to ambient temperature
  6. stirringThe mixture was stirred in an ice bath for about 2 h
  7. filtrationThe solid was collected by vacuum filtration
  8. washthe filter cake was rinsed with water (150 mL)
  9. customdried under vacuum for about 1 h
  10. filtrationfiltered
  11. washwashed with Et2O (1.5 L)
  12. customdried under vacuum
  13. customThe resulting solid was azeotroped with toluene (1 L)
  14. customto give a solid
  15. filtrationcollected by vacuum filtration
  16. washThe filter cake was washed with Et2O (500 mL)
  17. customdried under vacuum

Sources & evidence

ORD record
ord-9d59a7025b6042e5a1ba97143b1eb82f
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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