Hydrochloric Acid → Hydrochloric Acid

HRID 2176159Notes

Reaction equation

HRID 2176159 reaction equation
[ClH:1].Cl.[Br:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10]N)=[CH:6][CH:5]=1.[N:12]12[CH2:20][CH2:19][CH:16]([CH2:17][CH2:18]1)[C:15](=O)[CH2:14][CH2:13]2>C(O)(=O)C>[Br:3][C:4]1[CH:9]=[CH:8][C:7]2[NH:10][C:15]3[CH:16]4[CH2:19][CH2:20][N:12]([CH2:13][C:14]=3[C:6]=2[CH:5]=1)[CH2:18][CH2:17]4.[ClH:1]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 121574-Bromophenylhydrazine hydrochlorideHCID 64203071-Azabicyclo[3.2.2]nonan-4-one

Product 2

HCID 313Hydrochloric AcidHCID 672389759-bromo-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A solution of HCl in acetic acid (1 M, 30 mL) was added under nitrogen to a mixture of 4-bromophenylhydrazine hydrochloride (4.33 g, 19.37 mmol; Aldrich) and 1-azabicyclo[3.2.2]nonan-4-one (2.70 g, 19.37 mmol; Example 2A). The mixture was stirred at room temperature for 16 hours, then heated at 75° C. for 3 hours. The mixture was cooled to room temperature and concentrated under vacuum to remove most of the acetic acid. Anhydrous ethanol (100 mL) was added to the residue, and the mixture was heated at reflux for 10 minutes, then cooled to room temperature. The precipitate was collected by filtration, washed with ethanol (25 mL) and dried under vacuum to provide the title compound as its HCl salt (3.02 g). A portion of this salt (400 mg) was partitioned between 20% NaOH (25 mL) and chloroform (50 mL) and the organic phase was dried (sodium sulfate) and concentrated. The residue was crystallized from ethyl acetate-ethanol (5:1) to provide the free base of title compound: 1H NMR (300 MHz, methanol-d4) δ 2.14-2.36 (m, 4H), 3.17-3.25 (m, 1H), 3.33-3.45 (m, 2H), 3.45-3.65 (m, 2H), 4.54 (s, 2H), 7.18 (dd, J=8.8, 1.8 Hz, 1H), 7.24 (d, J=9.1 Hz, 1H), 7.51 ppm (d, J=2.4 Hz, 1H); MS(DCI) m/z 291/293 (M+H)+.

Workup

  1. temperatureheated at 75° C. for 3 hours
  2. temperatureThe mixture was cooled to room temperature
  3. concentrationconcentrated under vacuum
  4. customto remove most of the acetic acid
  5. additionAnhydrous ethanol (100 mL) was added to the residue
  6. temperaturethe mixture was heated
  7. temperatureat reflux for 10 minutes
  8. temperaturecooled to room temperature
  9. filtrationThe precipitate was collected by filtration
  10. washwashed with ethanol (25 mL)
  11. customdried under vacuum

Sources & evidence

ORD record
ord-b1627a63762649258f4ec79fac61d44f
Source dataset
uspto-grants-2015_06
Patent number
US09063126B2

Reaction notes

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