Hydrochloric Acid → 1H-Indazole-5-carboxaldehyde

HRID 1271026Notes

Reaction equation

HRID 1271026 reaction equation
[H-].[Na+].Br[C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][N:8]=[CH:7]2.C([Li])(CC)C.CN([CH:21]=[O:22])C.Cl.C(=O)(O)[O-].[Na+]>C1COCC1>[NH:9]1[C:10]2[C:6](=[CH:5][C:4]([CH:21]=[O:22])=[CH:12][CH:11]=2)[CH:7]=[N:8]1

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 7619295-bromo-1H-indazoleHCID 178418400CID 53628100

Product 1

HCID 212506441H-Indazole-5-carboxaldehyde

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

2.60 g (65.00 mmol) sodium hydride (60% in mineral oil) was added batchwise to a solution of 11.64 g (59.08 mmol) 5-bromo-1H-indazole in 150 mL THF under argon within 10 minutes and the mixture was stirred for 15 minutes at RT. The reaction mixture was cooled to −70° C. and within 30 minutes 100.00 mL (130.00 mmol) sec-butyllithium (1.3 M in cyclohexane) were added dropwise, while the temperature was kept below −60° C. The mixture was stirred for a further 2 h at −70° C. and then a solution of 20.00 mL (0.260 mol) DMF in 20 mL THF was added dropwise, while the temperature was kept below −50° C. The reaction mixture was slowly heated to RT and stirred for 16 h. Then the mixture was slowly cooled to 0° C. and slowly 180 mL of 2N aqueous HCl was added dropwise, the mixture was stirred for a further 15 minutes and the pH was adjusted to 9–10 with sat. aqueous sodium bicarbonate solution. The aqueous phase was exhaustively extracted with EtOAc, the combined org. phases were dried over magnesium sulphate and evaporated down i. vac. Column chromatography (silica gel, petroleum ether/EtOAc 1:1 v/v), trituration with hexane and drying i. vac. at 50° C. yielded the product.

Workup

  1. additionwere added dropwise, while the temperature
  2. customwas kept below −60° C
  3. stirringThe mixture was stirred for a further 2 h at −70° C.
  4. customwas kept below −50° C
  5. temperatureThe reaction mixture was slowly heated to RT
  6. stirringstirred for 16 h
  7. temperatureThen the mixture was slowly cooled to 0° C.
  8. stirringthe mixture was stirred for a further 15 minutes
  9. extractionThe aqueous phase was exhaustively extracted with EtOAc
  10. dry with materialphases were dried over magnesium sulphate
  11. customevaporated down i
  12. dry with materialColumn chromatography (silica gel, petroleum ether/EtOAc 1:1 v/v), trituration with hexane and drying i
  13. customat 50° C. yielded the product

Sources & evidence

ORD record
ord-f1bf4a6941d44342a39294f739b5219d
Source dataset
uspto-grants-2007_04
Patent number
US07205294B2

Reaction notes

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