Dimedone → HCID 178429602, compound

HRID 2167314Notes

Reaction equation

HRID 2167314 reaction equation
[CH3:1][C:2]1([CH3:10])[CH2:9][C:7](=O)[CH2:6][C:4](=[O:5])[CH2:3]1.[F:11][C:12]([F:27])([F:26])[C:13]1[CH:18]=[CH:17][C:16]([C:19]2[C:23]([CH:24]=O)=[CH:22][NH:21][N:20]=2)=[CH:15][CH:14]=1.[C:28]([O:34][CH:35]([CH3:37])[CH3:36])(=[O:33])[CH2:29][C:30]([CH3:32])=O.C([O-])(=O)C.[NH4+:42]>C(O)C.C(OCC)(=O)C>[CH3:32][C:30]1[NH:42][C:7]2[CH2:9][C:2]([CH3:1])([CH3:10])[CH2:3][C:4](=[O:5])[C:6]=2[CH:24]([C:23]2[C:19]([C:16]3[CH:17]=[CH:18][C:13]([C:12]([F:27])([F:26])[F:11])=[CH:14][CH:15]=3)=[N:20][NH:21][CH:22]=2)[C:29]=1[C:28]([O:34][CH:35]([CH3:37])[CH3:36])=[O:33]

Participants

7

Reactant 4

HCID 31358DimedoneHCID 68329Isopropyl acetoacetateHCID 517165Ammonium AcetateHCID 178519877HCID 178519877, compound

Product 1

HCID 178429602HCID 178429602, compoundYield 78%

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of dimedone (0.984 g, 4.1 mmole) in hot ethanol (12 ml) was added 3-(4-trifluoromethylphenyl)-4-pyrazolecarboxaldehyde (1.0 g, 4.1 mmole), isopropyl acetoacetate (0.6 ml, 4.1 mmole) and lastly ammonium acetate (0.616 g, 8.0 mmole). The mixture was maintained at reflux for 18 h. No precipitate formed from the reaction. The reaction mixture was stripped of the ethanol in vacuo. The crude material was dissolved in ethyl acetate and washed with water (2×) and the organic phase was separated and stripped in vacuo. The material was then dissolved in ethyl ether and after a few minutes a white precipitate started to form. The white suspension was then filtered over night as it was a slow viscous filtration. The white material was washed with more ether to provide the desired product (1.55 g, 78%) as a white powder. Rf=0.45 in ethyl acetate. 1H NMR (400 MHz; DMSO d6) δ 9.14 (bs, 1H); 8.34 (bd, 2H, J=7.4 Hz); 7.8 (bs, 2H); 7.35 (bs, 1H); 5.05 (bs, 1H); 4.65-4.55 (m, 1H); 3.35 (bs, 1H); 2.52 (bs, 1H); 2.46 (d, 1H, J=16.8 Hz); 2.32 (d, 1H, J=16.8 Hz); 2.23 (s, 3H); 2.20 (d, 1H, J=16.0 Hz); 2.04 (d, 1H, J=16.0 Hz); 1.05 (s, 3H); 0.93 (s, 3H); 0.7 (d, 3H, J=6.2 Hz); 0.55 (s, 3H, J=6.2 Hz). LC MS shows MH+ at 488; 2M+H at 975.

Workup

  1. temperatureThe mixture was maintained
  2. temperatureat reflux for 18 h
  3. customNo precipitate formed from the reaction
  4. washwashed with water (2×)
  5. customthe organic phase was separated
  6. dissolutionThe material was then dissolved in ethyl ether and after a few minutes a white precipitate
  7. customto form
  8. filtrationThe white suspension was then filtered over night as it
  9. filtrationa slow viscous filtration
  10. washThe white material was washed with more ether

Sources & evidence

ORD record
ord-6b3ac1514b6b44319c4e12f4459ae202
Source dataset
uspto-grants-2015_06
Patent number
US09045428B2

Reaction notes

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