Boron trifluoride etherate → 6,7-Dihydro-5h-benzo[6,7]cyclohepta[1,2-b]quinolin-8-amine

HRID 1071838Notes

Reaction equation

HRID 1071838 reaction equation
[C:1](#[N:9])[C:2]1[C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[NH2:4].[CH2:10]1[CH2:21][C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:13](=O)[CH2:12][CH2:11]1.B(F)(F)F.CCOCC.[OH-].[Na+]>C1(C)C=CC=CC=1.C(OCC)(=O)C>[CH:16]1[C:15]2[C:13]3=[N:4][C:3]4[C:2]([C:1]([NH2:9])=[C:12]3[CH2:11][CH2:10][CH2:21][C:20]=2[CH:19]=[CH:18][CH:17]=1)=[CH:8][CH:7]=[CH:6][CH:5]=4

Participants

7

Reactant 4

HCID 8000Boron trifluoride etherateHCID 14798Sodium HydroxideHCID 70003BenzosuberoneHCID 729132-Aminobenzonitrile

Product 1

HCID 4026666,7-Dihydro-5h-benzo[6,7]cyclohepta[1,2-b]quinolin-8-amineYield 86.1%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of anthranilonitrile (0.69 g, 5.8 mmol) and 1-benzosuberone (1.03 g, 0.96 mL, 6.4 mmol) in 25 mL anhydrous toluene was added boron trifluoride etherate (0.91 g, 0.81 mL, 6.4 mmol) slowly via syringe under a nitrogen atmosphere. The reaction was heated to reflux for 22 h. After cooling, sodium hydroxide solution (25 mL, 2 M, 50 mmol) was added. The reaction was heated to reflux for 23 h. After cooling, the reaction was diluted with ethyl acetate, washed with water (3×50 mL), brine (20 mL), dried over Na2SO4, filtered, and the solvent removed in vacuo. The residue (1.46 g) was dissolved in ethyl acetate:diethyl ether (1:1; 100 mL) with a trace of methanol (3 mL). To the solution was added 7 mL of a 1 N solution of HCl in diethyl ether. A resulting precipitate was collected by vacuum filtration and air-dried to provide the hydrochloride salt of the title compound as an off-white solid (1.30 g, 75%). MS (API+): M+1: 261 (100%); 1H NMR (300 MHz, DMSO-d6/TFA-d) d 2.13-2.29 (br m, 2H), 2.51-2.56 (br m, 2H), 2.56-2.75 (br m, 2H), 7.49 (d, J=7.0 Hz, 1H), 7.55-7.65 (m, 2H), 7.67-7.74 (m, 1H), 7.79 (d, J=7.8 Hz, 1H), 7.91-7.98 (m, 1H), 8.05 (d,J=8.7 Hz, 1H), 8.57 (d, J=8.7 Hz, 1H).

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux for 22 h
  3. temperatureAfter cooling
  4. temperatureThe reaction was heated
  5. temperatureto reflux for 23 h
  6. temperatureAfter cooling
  7. washwashed with water (3×50 mL), brine (20 mL)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. customthe solvent removed in vacuo
  11. dissolutionThe residue (1.46 g) was dissolved in ethyl acetate:diethyl ether (1:1; 100 mL) with a trace of methanol (3 mL)
  12. additionTo the solution was added 7 mL of a 1 N solution of HCl in diethyl ether
  13. filtrationA resulting precipitate was collected by vacuum filtration
  14. customair-dried

Sources & evidence

ORD record
ord-a2aec689c84b467992b3daf433b946d0
Source dataset
uspto-grants-2005_06
Patent number
US06906193B2

Reaction notes

Loading…