Sodium hydride → 1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-3-nitro-1H-pyrazole

HRID 546109Notes

Reaction equation

HRID 546109 reaction equation
[N+:1]([C:4]1[CH:8]=[CH:7][NH:6][N:5]=1)([O-:3])=[O:2].[H-].[Na+].Br[CH2:12][CH2:13][O:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16]>CN(C)C=O.C(OCC)(=O)C>[C:18]([Si:15]([CH3:17])([CH3:16])[O:14][CH2:13][CH2:12][N:6]1[CH:7]=[CH:8][C:4]([N+:1]([O-:3])=[O:2])=[N:5]1)([CH3:21])([CH3:20])[CH3:19]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 3608067(2-Bromoethoxy)-tert-butyldimethylsilaneHCID 178526745HCID 178526745, compound

Product 1

HCID 593449511-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-3-nitro-1H-pyrazoleYield 84.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-Nitro-1H-pyrazole (prepared in example 3, 250 mg, 2.21 mmol) was dissolved in anhydrous N,N-dimethylformamide (5 mL) and a 60% dispersion of sodium hydride in mineral oil (93 mg, 2.32 mmol) was added while stirring under nitrogen. After the effervescence ceased and the reaction stirred for an additional 10 min, (2-bromo-ethoxy)-tert-butyl-dimethyl-silane (598 mg, 2.50 mmol) was added. The reaction continued to stir under nitrogen for 2 h. The solution was diluted with ethyl acetate (200 mL), washed with water (2×75 mL), saturated aqueous brine solution (75 mL), dried over magnesium sulfate, filtered and concentrated in vacuo. Purification by flash column chromatography (Merck silica gel 60, 40-63 μm; 5% ethyl acetate/hexanes to 25% ethyl acetate/hexanes) afforded 1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-3-nitro-1H-pyrazole (508 mg, 84%) as a yellow oil: H1-NMR (400 MHz, DMSO-d6) δ 0.00 (6H, s), 0.86 (9H, s), 4.03 (2H, t, J=5.6 Hz), 4.40 (2H, t, J=5.2 Hz), 7.11 (1H, d, J=2.4 Hz), 8.06 (1H, d, J=2.4 Hz).

Workup

  1. stirringthe reaction stirred for an additional 10 min
  2. stirringto stir under nitrogen for 2 h
  3. washwashed with water (2×75 mL), saturated aqueous brine solution (75 mL)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification by flash column chromatography (Merck silica gel 60, 40-63 μm; 5% ethyl acetate/hexanes to 25% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-50cd962529e34a00ad6397eb7edcd402
Source dataset
uspto-grants-2011_05
Patent number
US07935699B2

Reaction notes

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