Hydrochloric Acid → HCID 178436662, compound

HRID 2099746Notes

Reaction equation

HRID 2099746 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([CH2:11][CH3:12])[CH:10]=1)[NH:7][N:6]=[C:5]2[CH3:13].[H-].[Na+].C([Li])(C)(C)C.CCCCC.Cl.[C:27](=O)(O)[O-:28].[Na+]>CN(C)C=O.O1CCCC1>[CH2:11]([C:9]1[CH:10]=[C:2]([CH:27]=[O:28])[CH:3]=[C:4]2[C:8]=1[NH:7][N:6]=[C:5]2[CH3:13])[CH3:12]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 8003PentaneHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 178418306HCID 178418306, compoundHCID 178435442HCID 178435442, compound

Product 1

HCID 178436662HCID 178436662, compoundYield 67%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

5-Bromo-7-ethyl-3-methylindazole (2.85 g, 11.9 mmol) and sodium hydride (0.31 g, 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 (15 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 (1.4 M, 18.7 mL, 2.0 equiv) was added over several minutes. After 1 h at −78° C., dimethylformamide (2.8 mL) was slowly added and the mixture allowed to warm to room temperature overnight. The solution was cooled to 0° C. and carefully treated with 1N hydrochloric acid (30 mL). After a few minutes, solid sodium bicarbonate was added until a pH of 9-10 was attained. The two layers were separated and the aqueous phase washed twice with ethyl acetate. The combined organic layers were washed with water (2×), brine (2×), dried over sodium sulfate, and concentrated. Column chromatography gave 1.5 g (67%) of pure material. LC/MS: tR=1.15 min, 189.12 (MH)+.

Workup

  1. additioncontaining a magnetic stir bar
  2. temperatureThe stirred mixture was cooled to −78° C.
  3. waitAfter 1 h at −78° C.
  4. temperatureto warm to room temperature overnight
  5. temperatureThe solution was cooled to 0° C.
  6. waitAfter a few minutes
  7. customThe two layers were separated
  8. washthe aqueous phase washed twice with ethyl acetate
  9. washThe combined organic layers were washed with water (2×), brine (2×)
  10. dry with materialdried over sodium sulfate
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-1f4935f74fd9429c8a544efad132df0f
Source dataset
uspto-grants-2009_08
Patent number
US07569578B2

Reaction notes

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