Water → 4-Nitro-2-{[2-(trimethylsilyl)ethoxy]methyl}-2H-indazole

HRID 2117321Notes

Reaction equation

HRID 2117321 reaction equation
[N+:1]([C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[CH:6]=[N:7][NH:8]2)([O-:3])=[O:2].[H-].[Na+].Cl[CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21].O>CN(C)C=O>[N+:1]([C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[CH:6]=[N:7][N:8]2[CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])([O-:3])=[O:2].[N+:1]([C:4]1[C:5]2[C:9]([CH:10]=[CH:11][CH:12]=1)=[N:8][N:7]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[CH:6]=2)([O-:3])=[O:2]

Participants

7

Reactant 4

HCID 962WaterHCID 180574-NitroindazoleHCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl ether

Product 2

HCID 691593504-Nitro-2-{[2-(trimethylsilyl)ethoxy]methyl}-2H-indazoleYield 42%HCID 691594204-Nitro-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-indazoleYield 38%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4nitroindazole (2.55 g, 15.6 mmol) in anhydrous dimethylformamide (20 ml) at room temperature was added sodium hydride (902 mg, 37.6 mmol, 2.4 eq, 60% dispersion in oil) portionwise. This was allowed to stir at room temperature for 10 minutes. 2-(Chloromethoxy)ethyl-trimethylsilane (3.3 ml, 18.8 mmol, 1.2 eq) was added and the reaction stirred at room temperature for a further 90 minutes. Water (30 ml) was added and the reaction extracted into diethyl ether (2×50 ml). The combined organic layers were washed with brine (2×50 ml), the layers separated and the organic layer dried over MgSO4, filtered and evaporated. The resulting oil was purified by column chromatography on silica eluting with 20% ethyl acetate in isohexane, to give 4-nitro-1-{[2-trimethylsilylethoxy]methyl}-1H-indazole (1.74 g, 38%) as the less polar product and 4-nitro-2-{[2-trimethylsilylethoxy]methyl}-2H-indazole (1.93 g, 42%) as the more polar product. 1H NMR—1-Substituted isomer—(360 MHz, CDCl3) δ 0.00 (9H, s), 0.94 (2H, t, J 8.4), 3.63 (2H, t, J 8.2), 5.89 (2H, s), 7.62 (1H, t, J 8.0), 8.03 (1H, d, J 8.3), 8.26 (1H, d, J 7.7), 8.71 (1H, s).

Workup

  1. stirringthe reaction stirred at room temperature for a further 90 minutes
  2. extractionthe reaction extracted into diethyl ether (2×50 ml)
  3. washThe combined organic layers were washed with brine (2×50 ml)
  4. customthe layers separated
  5. dry with materialthe organic layer dried over MgSO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe resulting oil was purified by column chromatography on silica eluting with 20% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-b44ba9bf042f4762b4ea3d68ff277a0f
Source dataset
uspto-grants-2008_10
Patent number
US07442701B2

Reaction notes

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