Pentane → 7-chloro-1H-indazole-5-carbaldehyde

HRID 1353526Notes

Reaction equation

HRID 1353526 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([Cl:11])[CH:10]=1)[NH:7][N:6]=[CH:5]2.[H-].[Na+].C([Li])(C)(C)C.CCCCC.S([O-])(O)(=O)=O.[K+].[C:30](=O)(O)[O-:31].[Na+]>CO.O.C(OCC)C.CN(C)C=O.O1CCCC1>[Cl:11][C:9]1[CH:10]=[C:2]([CH:30]=[O:31])[CH:3]=[C:4]2[C:8]=1[NH:7][N:6]=[CH:5]2

Participants

12

Reactant 6

HCID 8003PentaneHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 516920Potassium bisulfateHCID 211021945-Bromo-7-chloro-1H-indazoleHCID 178418306HCID 178418306, compound

Product 1

HCID 211022107-chloro-1H-indazole-5-carbaldehyde

Reagents, catalysts & solvents 5

HCID 887MethanolSolventHCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

5-Bromo-7-chloroindazole (2.0 g, 8.7 mmol) and sodium hydride (221 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 (30 mL) was added. The mixture was stirred at room temperature for 15 min, during which time it became homogeneous. 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 30 min at −78° C., the reaction was gradually warmed to −50° C., kept there for 15 min, 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 separatory funnel containing diethyl ether and water. The aqueous was made acidic by the addition of 1 M potassium hydrogen sulfate and neutralized by the addition of sodium bicarbonate. The aqueous was extracted with diethyl ether (3×) which was washed with water, then brine, dried over magnesium sulfate, and concentrated to give 1.7 g (100%) of nearly pure material. An analytically pure sample was obtained by recrystallization from hot methanol. 1H-NMR (CDCl3, 500 MHz) δ 7.97 (s, 1H), 8.20 (s, 1H), 8.30 (s, 1H), 10.02 (s, 1H).

Workup

  1. additioncontaining a magnetic stir bar
  2. temperatureThe stirred mixture was cooled to −78° C.
  3. waitAfter 30 min at −78° C.
  4. temperaturethe reaction was gradually warmed to −50° C.
  5. waitkept there for 15 min
  6. customrecooled to −78° C
  7. temperatureto warm to −50° C
  8. customThe solution was quickly transferred to a separatory funnel
  9. extractionThe aqueous was extracted with diethyl ether (3×) which
  10. washwas washed with water
  11. dry with materialbrine, dried over magnesium sulfate
  12. concentrationconcentrated
  13. customto give 1.7 g (100%) of nearly pure material

Sources & evidence

ORD record
ord-16da5dba42b34ac19724dd1f64044552
Source dataset
uspto-grants-2007_05
Patent number
US07220862B2

Reaction notes

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