Sodium hydride → 4-(3-Nitro-pyrazol-1-ylmethyl)-cyclohexanecarboxylic acid methyl ester

HRID 546110Notes

Reaction equation

HRID 546110 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]([CH:15]1[CH2:20][CH2:19][CH:18]([CH2:21]OS(C2C=CC(C)=CC=2)(=O)=O)[CH2:17][CH2:16]1)=[O:14]>CN(C)C=O.C(OCC)(=O)C>[CH3:11][O:12][C:13]([CH:15]1[CH2:20][CH2:19][CH:18]([CH2:21][N:6]2[CH:7]=[CH:8][C:4]([N+:1]([O-:3])=[O:2])=[N:5]2)[CH2:17][CH2:16]1)=[O:14]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 594606674-(Toluene-4-sulfonyloxymethyl)-cyclohexanecarboxylic acid methyl esterHCID 178526745HCID 178526745, compound

Product 1

HCID 671907474-(3-Nitro-pyrazol-1-ylmethyl)-cyclohexanecarboxylic acid methyl esterYield 37%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

The 3-Nitro-1H-pyrazole (prepared in example 3, 130 mg, 1.16 mmol) was dissolved in N,N-dimethylformamide (4 mL) and a 60% suspension of sodium hydride in mineral oil (50 mg, 1.25 mmol) was added. After the effervescence ceased and the reaction stirred for an additional 10 min, the 4-(toluene-4-sulfonyloxymethyl)-cyclohexanecarboxylic acid methyl ester (380 mg, 1.16 mmol) was added and the reaction was heated to 80° C. while stirring for 4 h. The reaction continued to stir under nitrogen for 2 h. The solution was diluted with ethyl acetate (100 mL), washed with saturated aqueous sodium bicarbonate solution (35 mL), 1.0 M aqueous hydrochloric acid solution (35 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 50% ethyl acetate/hexanes) afforded 4-(3-nitro-pyrazol-1-ylmethyl)-cyclohexanecarboxylic acid methyl ester (114 mg, 37%) as a yellow oil: H1-NMR (400 MHz, CDCl3) δ 1.00-1.12 (2H, m), 1.36-1.50 (2H, m), 1.68-1.78 (2H, m), 1.90-2.08 (3H, m), 2.20-2.30 (1H, m), 3.66 (3H, s), 4.03 (2H, d, J=7.2 Hz), 6.88 (2H, d, J=2.4 Hz), 7.40 (2H, d, J=8.4 Hz).

Workup

  1. stirringwhile stirring for 4 h
  2. stirringto stir under nitrogen for 2 h
  3. washwashed with saturated aqueous sodium bicarbonate solution (35 mL), 1.0 M aqueous hydrochloric acid solution (35 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 50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-8a5a2ff4df074e868ee936312ebadf74
Source dataset
uspto-grants-2011_05
Patent number
US07935699B2

Reaction notes

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