1-Nitropropane → 7-bromo-5-chloro-1H-indole-3-carbonitrile

HRID 913965

Reaction equation

HRID 913965 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([Cl:13])[CH:5]=[C:6]2[C:10]=1[NH:9][CH:8]=[C:7]2[CH:11]=O.P([O-])([O-])([O-])=O.[NH4+].[NH4+].[NH4+].[N+:22](CCC)([O-])=O>C(O)(=O)C>[Br:1][C:2]1[CH:3]=[C:4]([Cl:13])[CH:5]=[C:6]2[C:10]=1[NH:9][CH:8]=[C:7]2[C:11]#[N:22]

Participants

5

Reactant 3

HCID 79031-NitropropaneHCID 159282Ammonium phosphate, tribasicHCID 575461137-bromo-5-chloro-1H-indole-3-carbaldehyde

Product 1

HCID 575462207-bromo-5-chloro-1H-indole-3-carbonitrileYield 54.5%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A mixture of 7-bromo-5-chloro-1H-indole-3-carbaldehyde (0.80 g, 3.09 mmol), Ammonium phosphate, dibasic (1.269 mL, 15.47 mmol), and 1-nitropropane (0.276 mL, 3.09 mmol) in Acetic Acid (20 mL) was heated at reflux. The solvent was evaporated, the residue was taken up in aqueous sodium bicarbonate (300 mL) and extracted with ethyl acetate (3×20 mL). The organic layers were dried with MgSO4 and evaporated. The residue was purified by chromatography on SiO2 with 20%-25% ethyl acetate/hexanes to give 7-bromo-5-chloro-1H-indole-3-carbonitrile (0.43 g, 1.683 mmol, 54.4% yield) as a yellow solid. 1H-NMR (CDCl3, 400 MHz) δ 8.27 (bs, 1H), 7.79 (s, 1H), 7.72 (d, J=1.8 Hz, 1H), 7.49 (d, J=1.8 Hz, 1H). LC/MS (HPLC method 4): tR=3.12 min, 255.01(MH)+.

Workup

  1. temperaturewas heated
  2. temperatureat reflux
  3. customThe solvent was evaporated
  4. extractionextracted with ethyl acetate (3×20 mL)
  5. dry with materialThe organic layers were dried with MgSO4
  6. customevaporated
  7. customThe residue was purified by chromatography on SiO2 with 20%-25% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-b014e68c04824017b8e7a4fd2023d96d
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Linked notes

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