Bicyclo(2.2.1)heptan-2-one → 1,2,3,4-Tetrahydro-1,4-methanoacridin-9-amine

HRID 1590313Notes

Reaction equation

HRID 1590313 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[CH:14]2[CH2:15][C:16](=O)[CH:12]([CH2:13]2)[CH2:11]1.C([N-]C(C)C)(C)C.[Li+]>C1C=CC=CC=1.O1CCCC1.C1(C)C=CC(S(O)(=O)=O)=CC=1>[NH2:9][C:1]1[C:2]2[C:3]([N:4]=[C:11]3[C:10]=1[CH:14]1[CH2:13][CH:12]3[CH2:16][CH2:15]1)=[CH:5][CH:6]=[CH:7][CH:8]=2

Participants

7

Reactant 3

HCID 10345Bicyclo(2.2.1)heptan-2-oneHCID 729132-AminobenzonitrileHCID 2724682Lithium diisopropylamide

Product 1

HCID 143728181,2,3,4-Tetrahydro-1,4-methanoacridin-9-amineYield 25.4%

Reagents, catalysts & solvents 3

HCID 6101p-Toluenesulfonic acidCatalystHCID 241BenzeneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
25 °C

Procedure

A solution of anthranilonitrile (3.6 g, 30.0 mmole), norcamphor (3.3 g, 30.0 mmole) and para-toluenesulfonic acid (50 mg) in benzene (50 ml) was heated to reflux using a Dean Stark apparatus. After heating for 18 hours, the reaction mixture was then cooled (25° C.) and the separated water (about 1.5 ml) was withdrawn. The excess benzene was then removed under vacuum (1 mm Hg, 15 minutes). The oily residue thus obtained was dissolved in tetrahydrofuran (THF, 10 ml) and was cooled to 0° C. and a solution of lithium diisopropylamide in THF (1M, 36 ml, 36 mmole) was then added. This reaction mixture was then stirred at 0° C. for 3 hours. At the end of this period, the reaction mixture was quenched with 40 ml of water and was extracted with methylene chloride (200 ml). The resulting organic phase was washed with water (2×50 ml) and dried (anhydrous MgSO4). The methylene chloride was removed under vaccum to afford a residue which was loaded on a silica gel flash chromatography column. Elution with 5% methanol in methylene chloride containing 1% triethylamine afforded the title compound 1.6 g, 25%) as an oil which solidified on standing (m.p. 185°-186° C.). 1H-NMR (CDCl3, 300 MHz, δ): 2H, m, 1.22-1.42 ppm; 1H, d, 1.64 ppm (J=7.0 Hz); 1H, d, 1.86 ppm (J=6.0 Hz); 2H, m, 1.9-2.04 ppm; 2H, bd, 3.46 ppm; 2H, bs, 4.49 ppm; 1H, t, 7.38 ppm (J=6.0 Hz); 1H, t, 7.55 ppm (J=6.0 Hz); 1H, d, 7.67 ppm (J=6.0 Hz); 1H, d, 7.92 ppm (J=6.0 Hz).

Workup

  1. temperatureto reflux
  2. temperatureAfter heating for 18 hours
  3. customthe separated water (about 1.5 ml) was withdrawn
  4. customThe excess benzene was then removed under vacuum (1 mm Hg, 15 minutes)
  5. customThe oily residue thus obtained
  6. temperaturewas cooled to 0° C.
  7. customAt the end of this period, the reaction mixture was quenched with 40 ml of water
  8. extractionwas extracted with methylene chloride (200 ml)
  9. washThe resulting organic phase was washed with water (2×50 ml)
  10. dry with materialdried (anhydrous MgSO4)
  11. customThe methylene chloride was removed under vaccum
  12. customto afford a residue which
  13. washElution with 5% methanol in methylene chloride containing 1% triethylamine

Sources & evidence

ORD record
ord-2248bc5e48dd4e07847a44a940dac331
Source dataset
uspto-grants-1993_04
Patent number
US05202440

Reaction notes

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