Dimedone → HCID 22461273, compound

HRID 1937624Notes

Reaction equation

HRID 1937624 reaction equation
[CH3:1][C:2]([CH3:11])([CH3:10])[C:3](=O)[CH2:4]C(OC)=O.[N:12]([O-])=O.[Na+].O.O.O.C([O-])(=O)C.[Na+].[CH3:24][C:25]1([CH3:33])[CH2:30][C:29](=[O:31])[CH2:28][C:27](=O)[CH2:26]1>O.C(O)(=O)CC.[Zn].CC(O)=O>[CH3:33][C:25]1([CH3:24])[CH2:26][C:27]2[NH:12][CH:4]=[C:3]([C:2]([CH3:11])([CH3:10])[CH3:1])[C:28]=2[C:29](=[O:31])[CH2:30]1

Participants

9

Reactant 4

HCID 31358DimedoneHCID 99597Methyl pivaloylacetateHCID 23665404Sodium Acetate TrihydrateHCID 23668193Sodium Nitrite

Product 1

HCID 22461273HCID 22461273, compound

Reagents, catalysts & solvents 4

HCID 23994ZincCatalystHCID 176Acetic AcidSolventHCID 962WaterSolvent2×HCID 1032Propionic AcidSolvent2×

Procedure

Methyl 4,4-dimethyl-3-oxopentanoate (20 g, 0.13 mol) and AcOH (48 mL) were cooled to 10° C. and a solution of NaNO2 (12.3 g, 0.19 mol) in water (48 mL) was added dropwise to the stirred mixture, maintaining the temperature below 20° C. After addition the mixture was warmed to room temperature and stirred for 2 h. The mixture was then extracted with DCM (3×100 mL). The combined organic layers were evaporated and the residue taken up in ether. The ethereal layer was washed with water (100 mL), separated and dried (Na2SO4). The resultant yellow gum (22.7 g, 96%) was used without further purification. 1H NMR (250 MHz, CDCl3) δ 1.23 (9H,s), 3.89 (3H,s), 9.00-10.00 (1H,br s). Sodium acetate trihydrate (20.6 g, 0.15 mol) and 5,5-dimethyl-1,3-cyclohexandione (16.9 g, 0.12 mol) in propionic acid (140 mL) were heated to 150° C. A solution of the oxime (22.7 g, 0.12 mol) in propionic acid (70 mL) was added via a dropping funnel, whilst simultaneously adding zinc dust (12 g) over 20 min. The solution was heated at reflux for 24 h after which time it was poured into water. The resultant solid was collected by filtration then triturated with ether. The colourless solid (3.7 g, 14%) was collected by filtration. 1H NMR (360 MHz, CDCl3) δ 1.10 (6H,s), 1.35 (9H,s), 2.35 (2H,s), 2.64 (2H,s), 6.43 (1H,d,J=2.2 Hz), 7.80-8.14 (1H,br s). MS (ES+) 220 (M+1).

Workup

  1. temperaturemaintaining the temperature below 20° C
  2. additionAfter addition the mixture
  3. extractionThe mixture was then extracted with DCM (3×100 mL)
  4. customThe combined organic layers were evaporated
  5. washThe ethereal layer was washed with water (100 mL)
  6. customseparated
  7. dry with materialdried (Na2SO4)
  8. customThe resultant yellow gum (22.7 g, 96%) was used without further purification
  9. temperatureThe solution was heated
  10. temperatureat reflux for 24 h after which time it
  11. filtrationThe resultant solid was collected by filtration
  12. customthen triturated with ether
  13. filtrationThe colourless solid (3.7 g, 14%) was collected by filtration

Sources & evidence

ORD record
ord-45f0bcd6b0f34ea28c12f79c87d0bd8d
Source dataset
uspto-grants-2002_05
Patent number
US06395766B1

Reaction notes

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