Hydrochloric Acid → HCID 20430314, compound

HRID 1014338Notes

Reaction equation

HRID 1014338 reaction equation
C([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:13][CH3:14])[CH:11]=2)[CH2:6][CH2:5]1)(=O)C.[N+:15]([O-])([OH:17])=[O:16].Cl>C(OC(=O)C)(=O)C>[CH3:14][O:13][C:10]1[CH:11]=[C:12]2[C:7]([CH2:6][CH2:5][NH:4]2)=[CH:8][C:9]=1[N+:15]([O-:17])=[O:16]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 944Nitric AcidHCID 594419921-(2,3-Dihydro-6-methoxy-1H-indol-1-yl)ethanone

Product 1

HCID 20430314HCID 20430314, compoundYield 54%

Reagents, catalysts & solvents 1

HCID 7918Acetic AnhydrideSolvent

Procedure

To a solution of 1-acetyl-6-(methyloxy)-2,3-dihydro-1H-indole (2.0 g, 10.5 mmol) in acetic anhydride (150 mL) at 0° C. was added 70% nitric acid (1.03 g, 11.5 mmol) via a dropwise addition. After stirring the reaction at 0° C. for 2 hrs, the contents were allowed to warm to rt, the precipitate was filtered and washed with water. The filtrate was neutralized with 5.0 M NaOH, extracted with ethyl acetate (2×200 mL). The organic layers were combined, adsorbeded onto silica gel and purified by column chromatography (DCM to 2% MeOH/DCM). The derived residue was subsequently dissolved in methanol (200 mL), followed by the addition of 4M HCl(29 mL, 116 mmol). After heating at 60° C. for 3 hrs, the solvent was removed by rotary evaporation, the residue redissolved in THF (300 mL), washed with saturated NaHCO3 (300 mL) and the aqueous layer was extracted with THF (200 mL). The combined organic layers were filtered through a cotton plug, concentrated under reduced pressure, and placed under high vacuum for several hours to give 6-(methyloxy)-5-nitro-2,3-dihydro-1H-indole (1.1 g, 54% over two steps). ESIMS (M+H)+=195. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.90 (t, J=8.42 Hz, 2 H) 3.58 (t, J=8.52 Hz, 2 H) 3.75-3.79 (m, 3 H) 6.10 (s, 1 H) 7.14 (s, 1 H) 7.65 (s, 1H).

Workup

  1. additionvia a dropwise addition
  2. customthe reaction at 0° C. for 2 hrs
  3. filtrationthe precipitate was filtered
  4. washwashed with water
  5. extractionextracted with ethyl acetate (2×200 mL)
  6. custompurified by column chromatography (DCM to 2% MeOH/DCM)
  7. dissolutionThe derived residue was subsequently dissolved in methanol (200 mL)
  8. temperatureAfter heating at 60° C. for 3 hrs
  9. customthe solvent was removed by rotary evaporation
  10. dissolutionthe residue redissolved in THF (300 mL)
  11. washwashed with saturated NaHCO3 (300 mL)
  12. extractionthe aqueous layer was extracted with THF (200 mL)
  13. filtrationThe combined organic layers were filtered through a cotton plug
  14. concentrationconcentrated under reduced pressure
  15. waitplaced under high vacuum for several hours

Sources & evidence

ORD record
ord-039e83871a1f477588244f8769d1ee53
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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