Cesium carbonate → Ethyl 1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazole-4-carboxylate

HRID 548107Notes

Reaction equation

HRID 548107 reaction equation
[NH:1]1[CH:5]=[C:4]([C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH:3]=[N:2]1.Cl[CH2:12][C:13]1[C:14]([CH3:19])=[N:15][O:16][C:17]=1[CH3:18].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.Cl>[CH3:19][C:14]1[C:13]([CH2:12][N:1]2[CH:5]=[C:4]([C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH:3]=[N:2]2)=[C:17]([CH3:18])[O:16][N:15]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 88246Isoxazole, 4-(chloromethyl)-3,5-dimethyl-HCID 142179ethyl 1H-pyrazole-4-carboxylate

Product 1

HCID 57944988Ethyl 1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazole-4-carboxylateYield 80.2%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 6228DimethylformamideSolvent

Procedure

Ethyl 1H-pyrazole-4-carboxylate (4.2 g, 30 mmol), 4-(chloromethyl)-3,5-dimethylisoxazole (5.1 g, 35 mmol), and cesium carbonate (9.8 g, 30 mmol), in DMF (50 mL), were stirred at 80° C. for 12 hours. The reaction was cooled to ambient temperature, diluted with 0.1 N HCl (150 mL) and extracted with ethyl acetate (3×, 75 mL). The combined organic extracts were dried over sodium sulfate and concentrated on the rotovap. The solid product was triturated with ethyl acetate/hexanes (1/9) and collected by filtration to afford ethyl 1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazole-4-carboxylate (6 g, 80%) as a white solid. 1H NMR (CDCl3, 400 MHz): δ1.34 (t, J=7.2 Hz, 3H), 2.19 (s, 3H), 2.43 (s, 3H), 4.29 (q, J=7.2 Hz, 2H), 5.06 (s, 2H), 7.77 (s, 1H), 7.91 (s, 1H).

Workup

  1. extractionextracted with ethyl acetate (3×, 75 mL)
  2. dry with materialThe combined organic extracts were dried over sodium sulfate
  3. concentrationconcentrated on the rotovap
  4. customThe solid product was triturated with ethyl acetate/hexanes (1/9)
  5. filtrationcollected by filtration

Sources & evidence

ORD record
ord-a13d61e81a9b49e9b35fa5dc6a34d5b1
Source dataset
uspto-grants-2011_05
Patent number
US07939671B2

Reaction notes

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