Potassium Carbonate → 1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-3-nitro-1H-pyrazole

HRID 19016Notes

Reaction equation

HRID 19016 reaction equation
[N+:1]([C:4]1[CH:8]=[CH:7][NH:6][N:5]=1)([O-:3])=[O:2].[CH3:9][C:10]1([CH3:27])[O:14][C@H:13]([CH2:15]OS(C2C=CC(C)=CC=2)(=O)=O)[CH2:12][O:11]1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.C(OCC)(=O)C>[CH3:9][C:10]1([CH3:27])[O:14][C@H:13]([CH2:15][N:6]2[CH:7]=[CH:8][C:4]([N+:1]([O-:3])=[O:2])=[N:5]2)[CH2:12][O:11]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 2723760(S)-(+)-2,2-Dimethyl-1,3-dioxolan-4-ylmethyl p-ToluenesulfonateHCID 178526745HCID 178526745, compound

Product 1

HCID 593449371-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-3-nitro-1H-pyrazoleYield 72%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

A solution of 3-nitro-1H-pyrazole (prepared as in Example 5, 12.0 g, 106 mmol) in N,N-dimethylformamide (150 mL) was treated with toluene-4-sulfonic acid (S)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl ester (25.5 g, 89.0 mmol), and potassium carbonate (24.5 g, 178 mmol). The reaction mixture was stirred for 6 h at 90° C., under nitrogen. The reaction mixture was diluted with ethyl acetate, washed with water twice, a saturated sodium chloride solution and dried over sodium sulfate. The organic layer was concentrated, and the crude product was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 330 g, 5% to 30% ethyl acetate/hexanes) to afford 1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-3-nitro-1H-pyrazole (14.5 g, 72%) as light yellow oil: LR-ES-MS m/z calculated for C9H13N3O4 [M]+ 227, observed [M+H]+ 228. 1H NMR (300 MHz, CDCl3) δ ppm 1.35 (s, 3H), 1.40 (s, 3H), 3.77 (dd, J=8.8, 5.7 Hz, 1H), 4.13 (dd, J=8.8, 6.6 Hz, 1H), 4.27 (dd, J=14.0, 6.6 Hz, 1H), 4.39 (dd, J=14.0, 3.6 Hz, 1H), 4.45-4.59 (m, 1H), 6.92 (d, J=2.4 Hz, 1H), 7.59 (d, J=2.4 Hz, 1H)

Workup

  1. washwashed with water twice
  2. dry with materiala saturated sodium chloride solution and dried over sodium sulfate
  3. concentrationThe organic layer was concentrated
  4. customthe crude product was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 330 g, 5% to 30% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-7cc451c997fb4548876b2a95ef76272b
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

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