Cesium carbonate → HCID 24225555, compound

HRID 2094993Notes

Reaction equation

HRID 2094993 reaction equation
[N+:1]([C:4]1[CH:5]=[N:6][NH:7][CH:8]=1)([O-:3])=[O:2].C(=O)([O-])[O-].[Cs+].[Cs+].Cl[CH2:16][C:17]1[C:18]([CH3:23])=[N:19][O:20][C:21]=1[CH3:22]>CN(C=O)C.O>[CH3:23][C:18]1[C:17]([CH2:16][N:6]2[CH:5]=[C:4]([N+:1]([O-:3])=[O:2])[CH:8]=[N:7]2)=[C:21]([CH3:22])[O:20][N:19]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 163764-nitro-1H-pyrazoleHCID 88246Isoxazole, 4-(chloromethyl)-3,5-dimethyl-

Product 1

HCID 24225555HCID 24225555, compoundYield 67.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

1H-pyrazole (10 g, 147 mmol) was added in small portions to concentrated H2SO4 (100 mL), cooled to 0° C. via an ice/water bath, maintaining the internal reaction temperature below 40° C. Concentrated HNO3 (10 mL) was carefully added, dropwise, to the reaction mixture maintaining the internal reaction temperature below 55° C. The reaction was then heated to 55° C. and stirred for 5 hours. The mixture was cooled to 0° C. and carefully made basic (pH˜8) with aqueous NaOH solution (110 g NaOH in 150 mL H2O) until a white precipitate formed, carefully ensuring the internal temperature of the solution remain below 40° C. The white solid was collected by filtration and washed with ethyl acetate/hexanes (1/3) then dried en vacuo to afford 4-nitro-1H-pyrazole (7 g, 42%, isolated yield). 13C NMR (DMSO-d6, 137.0, 126.4. To 4-nitro-1H-pyrazole (9 g, 80 mmol) in DMF (100 mL)100 MHz) δ was added cesium carbonate (26 g, 80 mmol) followed by the addition of 4-(chloromethyl)-3,5-dimethylisoxazole (12.3 g, 85 mmol). The reaction mixture was stirred in DMF (100 mL) at 80° C. for 30 minutes, then cooled, diluted with H2O (150 mL) and extracted with ethyl acetate (3×, 75 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated. The residue was taken up in ethyl acetate (200 mL) and washed with H2O (2×, 100 mL). The organic layer was dried over sodium sulfate, filtered and concentrated. The solid product was triturated with ethyl acetate/hexanes(1/9) and collected by filtration. The product was dried under high vacuum to afford 3,5-dimethyl-4-((4-nitro-1H-pyrazol-1-yl)methyl)isoxazole (12 g, 67%) as a light yellow solid. 1H NMR (CDCl3, 400 MHz): δ 2.23 (s, 3H), 2.46 (s, 3H), 5.08 (s, 2H), 8.02 (s, 1H), 8.08 (s, 1H).

Workup

  1. temperaturecooled
  2. extractionextracted with ethyl acetate (3×, 75 mL)
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. washwashed with H2O (2×, 100 mL)
  7. dry with materialThe organic layer was dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe solid product was triturated with ethyl acetate/hexanes(1/9)
  11. filtrationcollected by filtration
  12. customThe product was dried under high vacuum

Sources & evidence

ORD record
ord-572469f5fbcd441cba807b9d27fa74ae
Source dataset
uspto-grants-2013_05
Patent number
US08445692B2

Reaction notes

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