Sodium hydride → HCID 67188885, compound

HRID 546101Notes

Reaction equation

HRID 546101 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:25])[C:14]1[CH:19]=[CH:18][C:17]([CH:20](Br)[CH2:21][CH2:22][CH3:23])=[CH:16][CH:15]=1>CN(C)C=O>[CH3:11][O:12][C:13](=[O:25])[C:14]1[CH:19]=[CH:18][C:17]([CH:20]([N:6]2[CH:7]=[CH:8][C:4]([N+:1]([O-:3])=[O:2])=[N:5]2)[CH2:21][CH2:22][CH3:23])=[CH:16][CH:15]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 22399772Methyl 4-(1-bromobutyl)benzoateHCID 178526745HCID 178526745, compound

Product 1

HCID 67188885HCID 67188885, compoundYield 43.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

3-Nitro-1H-pyrazole (prepared in example 3, 113 mg, 1.00 mmol) was dissolved in anhydrous N,N-dimethylformamide (2.5 mL) and a 60% dispersion of sodium hydride in mineral oil (40 mg, 1.00 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 4-(1-bromo-butyl)-benzoic acid methyl ester (261 mg, 0.97 mmol) was added. The reaction continued to stir under nitrogen at 0° C. for 20 min. The ice bath was removed and the reaction continued to stir at 25° C. for 16 h. The reaction was diluted with ethyl acetate (100 mL), washed with water (2×25 mL), saturated aqueous brine solution (2×10 mL), dried over magnesium sulfate and concentrated in vacuo to give an oil. Purification by ISCO flash column chromatography (Teledyne Isco RediSep Flash Column 40 g; 0% ethyl acetate/hexanes to 20% ethyl acetate/hexanes) afforded 4-[1-(3-nitro-pyrazol-1-yl)-butyl]-benzoic acid methyl ester (127 mg, 42%) as a white waxy solid: ESI-LRMS m/e calcd for C15H17N3O4 [M+] 303.1, found 304.5 [M+H+].

Workup

  1. stirringthe reaction stirred for an additional 25 min
  2. stirringto stir under nitrogen at 0° C. for 20 min
  3. customThe ice bath was removed
  4. stirringto stir at 25° C. for 16 h
  5. additionThe reaction was diluted with ethyl acetate (100 mL)
  6. washwashed with water (2×25 mL), saturated aqueous brine solution (2×10 mL)
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated in vacuo
  9. customto give an oil
  10. customPurification by ISCO flash column chromatography (Teledyne Isco RediSep Flash Column 40 g; 0% ethyl acetate/hexanes to 20% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-b8797f43c0864475a2675445e58437c8
Source dataset
uspto-grants-2011_05
Patent number
US07935699B2

Reaction notes

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