Sodium hydride → HCID 67191930, compound

HRID 546088Notes

Reaction equation

HRID 546088 reaction equation
[N+:1]([C:4]1[CH:8]=[CH:7][NH:6][N:5]=1)([O-:3])=[O:2].[H-].[Na+].[CH3:11][O:12][C:13](=[O:22])[C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([CH2:20]Br)[CH:15]=1>CN(C)C=O.C(OCC)(=O)C>[CH3:11][O:12][C:13](=[O:22])[C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([CH2:20][N:6]2[CH:7]=[CH:8][C:4]([N+:1]([O-:3])=[O:2])=[N:5]2)[CH:15]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 517981Methyl 3-(bromomethyl)benzoateHCID 178526745HCID 178526745, compound

Product 1

HCID 67191930HCID 67191930, compoundYield 82.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

3-Nitro-1H-pyrazole (prepared in example 3, 1.00 g, 8.84 mmol) was dissolved in anhydrous N,N-dimethylformamide (15 mL) and a 60% dispersion of sodium hydride in mineral oil (423 mg, 10.61 mmol) was added while stirring under nitrogen. After the effervescence ceased and the reaction stirred for an additional 25 min, the reaction was chilled to 0° C. and the 3-bromomethyl-benzoic acid methyl ester (2.11 g, 9.20 mmol) was added. The reaction continued to stir under nitrogen at 0° C. for 20 min. The reaction was diluted with ethyl acetate (200 mL), washed with water (2×50 mL), saturated aqueous brine solution (2×20 mL), dried over magnesium sulfate and concentrated in vacuo to give an orange oil. Purification by ISCO flash column chromatography (Teledyne Isco RediSep Flash Column 120 g; 10% ethyl acetate/hexanes to 60% ethyl acetate/hexanes) afforded 3-(3-nitro-pyrazol-1-ylmethyl)-benzoic acid methyl ester (1.90 g, 82%) as a white waxy solid: H1-NMR (400 MHz, CDCl3) δ 3.93 (3H, s), 5.42 (2H, s), 6.91 (1H, d, J=2.0 Hz), 7.42-7.48 (3H, m), 7.97 (1H, s), 8.03-8.04 (1H, m).

Workup

  1. stirringthe reaction stirred for an additional 25 min
  2. stirringto stir under nitrogen at 0° C. for 20 min
  3. washwashed with water (2×50 mL), saturated aqueous brine solution (2×20 mL)
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customto give an orange oil
  7. customPurification by ISCO flash column chromatography (Teledyne Isco RediSep Flash Column 120 g; 10% ethyl acetate/hexanes to 60% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-91aa18495d8b459cb85fc6409fb58c81
Source dataset
uspto-grants-2011_05
Patent number
US07935699B2

Reaction notes

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