Cesium carbonate → (1-(2-bromoethyl)-3-nitro-1H-pyrazol-5-yl)methanol

HRID 1907785Notes

Reaction equation

HRID 1907785 reaction equation
[N+:1]([C:4]1[CH:8]=[C:7]([CH2:9][OH:10])[NH:6][N:5]=1)([O-:3])=[O:2].C(=O)([O-])[O-].[Cs+].[Cs+].[Br:17][CH:18](Br)[CH3:19].OP([O-])(O)=O.[K+]>O.C(OCC)(=O)C.CN(C=O)C>[Br:17][CH2:18][CH2:19][N:6]1[C:7]([CH2:9][OH:10])=[CH:8][C:4]([N+:1]([O-:3])=[O:2])=[N:5]1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 112011,1-DibromoethaneHCID 516951Monobasic potassium phosphateHCID 178526711HCID 178526711, compound

Product 1

HCID 58043832(1-(2-bromoethyl)-3-nitro-1H-pyrazol-5-yl)methanolYield 86%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
104 °C

Procedure

A 1-L three-necked round-bottomed flask equipped with a mechanical stirrer and thermoregulator was purged with nitrogen and charged with (3-nitro-1H-pyrazol-5-yl)methanol (25.0 g, 175 mmol), DMF (250 mL), and cesium carbonate (70.0 g, 215 mmol) was heated at 104° C. for 5 min. The reaction mixture was then cooled to 0° C. using an ice/acetone bath and dibromoethane (329 g, 1.75 mol) was added portionwise (no exotherm). The reaction was stirred at 0° C. for 1 then at room temperature for 4 h. After this time a solution of KH2PO4 (40 g) in water (400 mL) was added slowly. The reaction mixture stirred at room temperature for 30 min. Ethyl acetate (450 mL) was added and the aqueous layer was separated and extracted with ethyl acetate (2×100 mL). The combined organic layers were washed with water (200 mL), brine (200 mL), dried over sodium sulfate, and the drying agent was removed by filtration. The filtrate was concentrated under reduced pressure to afford an 86% yield (37.5 g) of crude (1-(2-bromoethyl)-3-nitro-1H-pyrazol-5-yl)methanol as an orange oil: 1H NMR (300 MHz, CDCl3) δ 6.85 (s, 1H), 4.82 (d, 2H, J=5.4 Hz), 4.66 (t, 2H, J=6.3 Hz), 3.83 (t, 2H, J=6.3 Hz); MS (ESI+) m/z 249.9 (M+H). This material was used in the following step directly.

Workup

  1. customA 1-L three-necked round-bottomed flask equipped with a mechanical stirrer
  2. customthermoregulator was purged with nitrogen
  3. temperatureThe reaction mixture was then cooled to 0° C.
  4. stirringThe reaction mixture stirred at room temperature for 30 min
  5. customthe aqueous layer was separated
  6. extractionextracted with ethyl acetate (2×100 mL)
  7. washThe combined organic layers were washed with water (200 mL), brine (200 mL)
  8. dry with materialdried over sodium sulfate
  9. customthe drying agent was removed by filtration
  10. concentrationThe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-31728181abe54ac997e7f02fff3ddada
Source dataset
uspto-grants-2013_12
Patent number
US08598174B2

Reaction notes

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