Nitric Acid → Ethyl 5-nitro-1H-indazole-3-carboxylate

HRID 600654

Reaction equation

HRID 600654 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([C:10]([O:12][CH2:13][CH3:14])=[O:11])=[N:2]1.[N+:15]([O-])([OH:17])=[O:16]>S(=O)(=O)(O)O>[N+:15]([C:6]1[CH:5]=[C:4]2[C:9](=[CH:8][CH:7]=1)[NH:1][N:2]=[C:3]2[C:10]([O:12][CH2:13][CH3:14])=[O:11])([O-:17])=[O:16]

Participants

4

Reactant 2

HCID 944Nitric AcidHCID 78251ethyl 1H-indazole-3-carboxylate

Product 1

HCID 12689368Ethyl 5-nitro-1H-indazole-3-carboxylateYield 53%

Reagents, catalysts & solvents 1

HCID 1118Sulfuric AcidSolvent2×

Conditions

Temperature
0 °C

Procedure

Ethyl indazole-3-carboxylate (73.7 mmol) was dissolved in 20 mL concentrated sulfuric acid and the reaction mixture was cooled to 0° C. A mixture of concentrated sulfuric acid (12 mL) and 70% nitric acid (12 mL) was added dropwise over the course of 1 h. The mixture was stirred for an additional 1 h at 0° C. and was poured onto of crushed ice (200 g). The solid was collected by vacuum filtration, washed with several portions of water and dried in vacuo. The dried solid was suspended in 250 mL acetonitrile and the mixture was heated at reflux for 2 h. The mixture was allowed to cool to room temperature and the solid was collected and dried in vacuo to provide ethyl 5-nitroindazole-3-carboxylate (53%) as a colorless solid. The acid, obtained by basic hydrolysis, was coupled with the bicyclobase according to procedure A.

Workup

  1. additionwas added dropwise over the course of 1 h
  2. filtrationThe solid was collected by vacuum filtration
  3. washwashed with several portions of water
  4. customdried in vacuo
  5. temperaturethe mixture was heated
  6. temperatureat reflux for 2 h
  7. temperatureto cool to room temperature
  8. customthe solid was collected
  9. customdried in vacuo

Sources & evidence

ORD record
ord-5fd1762151a448b684ac8773e75c30ba
Source dataset
uspto-grants-2011_03
Patent number
US07902217B2

Linked notes

Loading…