Hydrochloric Acid → Ethyl 3-chloro-6-nitroindazol-1-ylacetate

HRID 1464576

Reaction equation

HRID 1464576 reaction equation
[Cl:1][C:2]1[C:10]2[C:5](=[CH:6][C:7]([N+:11]([O-:13])=[O:12])=[CH:8][CH:9]=2)[NH:4][N:3]=1.[H-].[Na+].Br[CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19].Cl>CN(C=O)C.C(OCC)(=O)C.O>[Cl:1][C:2]1[C:10]2[C:5](=[CH:6][C:7]([N+:11]([O-:13])=[O:12])=[CH:8][CH:9]=2)[N:4]([CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])[N:3]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 7748Ethyl bromoacetateHCID 24758Sodium hydrideHCID 178526457HCID 178526457, compound

Product 1

HCID 19086706Ethyl 3-chloro-6-nitroindazol-1-ylacetateYield 56.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
5 °C

Procedure

3-chloro-6-nitroindazole (20 g) was dissolved in dry DMF (180cm3) and the solution cooled to 5° C. 50% sodium hydride (4.86 g) was added portionwise with stirring and cooling between 5° and 10° C. and then for an additional 15 minutes. Ethyl bromoacetate (16.91 g) was added slowly at 5° C., the reaction mixture warming to 30° C. The reaction mixture was then stirred at 20° C. for four hours. Water (lL) was added and the mixture acidified with diluted hydrochloric acid, shaken with ethyl acetate and filtered through hyflo. The organic phase was separated from the filtrate and the aqueous phase extracted (×2) with ethyl acetate. The combined organic phase was washed with water, dried (MgSO4) filtered and the solvent removed from the filtrate under vacuum. The residue was purified by flash chromatography (SiO2 ; hexane: TBME, 7:3 and then chloroform:ethyl acetate 95:5) to give ethyl 3-chloro-6-nitroindazol-1-ylacetate (16.25 g) as a pale yellow solid m.pt 109.1°-110.3° C.

Workup

  1. temperaturecooling between 5° and 10° C.
  2. temperaturethe reaction mixture warming to 30° C
  3. stirringThe reaction mixture was then stirred at 20° C. for four hours
  4. filtrationfiltered through hyflo
  5. customThe organic phase was separated from the filtrate
  6. extractionthe aqueous phase extracted (×2) with ethyl acetate
  7. washThe combined organic phase was washed with water
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. customthe solvent removed from the filtrate under vacuum
  11. customThe residue was purified by flash chromatography (SiO2

Sources & evidence

ORD record
ord-afbdf5edbd7e49f1a8c3810ab5fc418a
Source dataset
uspto-grants-1994_04
Patent number
US05306692

Linked notes

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