Pentane → 7-Ethyl-1H-indazole-5-carboxaldehyde

HRID 2355870Notes

Reaction equation

HRID 2355870 reaction equation
BrC1C=C2C(=C(CC)C=1)[NH:7][N:6]=[CH:5]2.[H-].[Na+].[C:15]([Li])([CH3:18])([CH3:17])[CH3:16].[CH3:20][CH2:21][CH2:22][CH2:23][CH3:24].S([O-])(O)(=O)=[O:26].[K+]>O.CN(C)C=O.O1CCCC1>[CH2:21]([C:22]1[CH:16]=[C:15]([CH:18]=[O:26])[CH:17]=[C:24]2[C:23]=1[NH:7][N:6]=[CH:5]2)[CH3:20]

Participants

9

Reactant 5

HCID 8003PentaneHCID 24758Sodium hydrideHCID 516920Potassium bisulfateHCID 211021955-bromo-7-ethyl-1H-indazoleHCID 178418306HCID 178418306, compound

Product 1

HCID 211022117-Ethyl-1H-indazole-5-carboxaldehyde

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

5-Bromo-7-ethyl-1H-indazole (2.0 g, 8.9 mmol) and sodium hydride (226 mg, 1.1 equiv.) were weighed into a flame-dried round-bottom flask containing a magnetic stir bar. Under a nitrogen atmosphere at room temperature, dry tetrahydrofuran (60 mL) was added. The mixture was stirred at room temperature for 15 min. The stirred mixture was cooled to −78° C. and a solution of tert-butyllithium in pentane (1.7 M, 10.5 mL, 2.0 equiv.) was added over several minutes. After 15 min at −78° C., the reaction was gradually warmed to −50° C., and recooled to −78° C. Dimethylformamide (2.8 mL) was slowly added and the mixture allowed to warm to −50° C. The solution was quickly transferred to a stirred solution of water 300 mL and 1 M potassium hydrogen sulfate (25 mL). The resulting suspension was extracted with diethyl ether, washed with water, then brine, dried over magnesium sulfate, and concentrated. Column chromatography gave 160 mg (10%) as a white solid. 1H-NMR (CD3OD, 500 MHz) δ 1.38 (t, J=7.6, 3H), 2.98 (q, J=7.6, 2H), 7.71 (s, 1H), 8.22 (s, 1H), 8.24 (s, 1H), 9.96 (s, 1H). Mass spec.: 175.08 (MH)+.

Workup

  1. additioncontaining a magnetic stir bar
  2. temperatureThe stirred mixture was cooled to −78° C.
  3. waitAfter 15 min at −78° C.
  4. temperaturethe reaction was gradually warmed to −50° C.
  5. customrecooled to −78° C
  6. temperatureto warm to −50° C
  7. extractionThe resulting suspension was extracted with diethyl ether
  8. washwashed with water
  9. dry with materialbrine, dried over magnesium sulfate
  10. concentrationconcentrated
  11. customColumn chromatography gave 160 mg (10%) as a white solid

Sources & evidence

ORD record
ord-4665cbab12184415b048b2ceae1a2bc8
Source dataset
uspto-grants-2010_07
Patent number
US07754732B2

Reaction notes

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