Hydrochloric Acid → 8-Bromo-6-methyl-3,4,5,6-tetrahydro-1H-2,5-methanoazepino[4,3-b]indole

HRID 1521463Notes

Reaction equation

HRID 1521463 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([N:8]([CH3:10])N)[CH:5]=[CH:6][CH:7]=1.[N:11]12[CH2:18][CH:15]([CH2:16][CH2:17]1)[C:14](=O)[CH2:13][CH2:12]2.Cl>C(O)(C)C>[Br:1][C:2]1[CH:7]=[CH:6][C:5]2[C:13]3[CH2:12][N:11]4[CH2:18][CH:15]([CH2:16][CH2:17]4)[C:14]=3[N:8]([CH3:10])[C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 100804071-Azabicyclo(3.2.1)octan-4-oneHCID 534011811-(3-Bromophenyl)-1-methylhydrazine

Product 1

HCID 580794278-Bromo-6-methyl-3,4,5,6-tetrahydro-1H-2,5-methanoazepino[4,3-b]indoleYield 95%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

1-(3-Bromophenyl)-1-methylhydrazine (0.48 g, 2.3 mmol) and 1-azabicyclo[3.2.1]octan-4-one (0.33 g, 2.6 mmol) were dissolved in isopropanol (3 mL), and concentrated aqueous HCl (0.75 mL) was added. The reaction mixture was heated to reflux for 18 h, concentrated and basified using 2 N NaOH. The aqueous layer was extracted with methylene chloride (3×). The combined organic extracts were dried over Na2SO4, filtered and concentrated to dryness. The residue was purified by flash column chromatography (silica gel, 10%-100% solvent mixture B in ethyl acetate; solvent mixture B=80:18:2 ethyl acetate/methanol/concentrated ammonium hydroxide) to give the title compound (634 mg, 95%) as a yellow semisolid: 1H NMR (300 MHz, CDCl3) δ 7.42 (d, J=2.5 Hz, 1H), 7.20 (d, J=13.5 Hz, 1H), 7.14 (d, J=13.5 Hz, 1H), 4.40 (d, J=26.5 Hz, 1H), 3.72 (d, J=26.0 Hz, 1H), 3.63 (s, 3H), 3.34-3.25 (m, 1H), 3.20-3.17 (m, 2H), 3.17-3.13 (m, 1H), 2.97-2.92 (m, 1H), 2.87-2.76 (m, 2H).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 18 h
  3. concentrationconcentrated
  4. extractionThe aqueous layer was extracted with methylene chloride (3×)
  5. dry with materialThe combined organic extracts were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated to dryness
  8. customThe residue was purified by flash column chromatography (silica gel, 10%-100% solvent mixture B in ethyl acetate; solvent mixture B=80:18:2 ethyl acetate/methanol/concentrated ammonium hydroxide)

Sources & evidence

ORD record
ord-ca35c3b7e43843b58c7f9ebf68280228
Source dataset
uspto-grants-2015_07
Patent number
US09073925B2

Reaction notes

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