Phthalic Anhydride → N-Methyl-6-amino-4a-(3-methoxyphenyl)-8a-methyloctahydroisoquinoline Phthalimide

HRID 1453972Notes

Reaction equation

HRID 1453972 reaction equation
[CH3:1][N:2]1[CH2:11][CH2:10][C:9]2([C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH3:19])[CH:13]=3)[C:4]([CH3:21])([CH2:5][CH2:6][CH:7]([NH2:20])[CH2:8]2)[CH2:3]1.[C:22]1(=O)[O:27][C:25](=[O:26])[C:24]2=[CH:28][CH:29]=[CH:30][CH:31]=[C:23]12>C1(C)C=CC=CC=1>[C:22]1(=[O:27])[NH:2][C:25](=[O:26])[C:24]2=[CH:28][CH:29]=[CH:30][CH:31]=[C:23]12.[CH3:1][N:2]1[CH2:11][CH2:10][C:9]2([C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH3:19])[CH:13]=3)[C:4]([CH3:21])([CH2:5][CH2:6][CH:7]([NH2:20])[CH2:8]2)[CH2:3]1

Participants

4

Reactant 2

HCID 6811Phthalic AnhydrideHCID 68828064N-Methyl-6-amino-4a-(3-methoxyphenyl)-8a-methyloctahydroisoquinoline

Product 1

HCID 68828063N-Methyl-6-amino-4a-(3-methoxyphenyl)-8a-methyloctahydroisoquinoline PhthalimideYield 175.8%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Amine 20 (1.70 g, 0.0058 mol) was dissolved in anhydrous toluene (100 mL) followed by the addition of phthalic anhydride (2.61 g, 0.018 mol), and the mixture was refluxed with Dean-Stark trap overnight. The solution was then cooled, washed with 1 N NaOH (3×50 mL) and water. The organic layer was collected, dried (Na2SO4) and the solvent removed under reduced pressure yielding crude product. The crude product was purified by flash chromatography (30% EtOAc/hexanes on neutral Al2O3 Brockman activity II-III) to afford 2.22 g (90%) of 21 as a white solid: LCMS (ESI): m/z 419.9 (M+H)+; 1H NMR (CDCl3, 300 MHz) δ 7.80-7.83 [m, 2H], 7.68-7.71 [m, 2H], 7.23-7.27 [m, 3H], 6.77-6.79 [m, 1H], 4.81 [m, 1H], 3.85 [s, 3H], 3.28 [t, J=12 Hz, 1H], 3.01 [d, J=12 Hz, 1H], 2.83-2.85 [m, 1H], 2.65-2.81 [m, 1H], 2.40-2.47 [m, 2H], 2.37 [s, 3H], 2.16-2.20 [m, 1H], 1.89 [ddd, J1=J2=15 Hz, J3=6 Hz, 1H], 1.48-1.58 [m, 3H], 1.33-1.39 [m, 1H], 1.26 [s, 3H]; 13CNMR (CDCl3, 300 MHz) δ 168.8, 159.2, 148.4, 134.1, 132.4, 128.7, 123.3, 121.8, 116.0, 111.0, 64.8, 55.5, 52.9, 47.8, 47.2, 43.8, 36.7, 35.6, 34.1, 26.7, 24.3.

Workup

  1. temperaturethe mixture was refluxed with Dean-Stark trap overnight
  2. temperatureThe solution was then cooled
  3. washwashed with 1 N NaOH (3×50 mL) and water
  4. customThe organic layer was collected
  5. dry with materialdried (Na2SO4)
  6. customthe solvent removed under reduced pressure
  7. customyielding crude product
  8. customThe crude product was purified by flash chromatography (30% EtOAc/hexanes on neutral Al2O3 Brockman activity II-III)

Sources & evidence

ORD record
ord-a6487c323f2b4c74b1a1758aa5420f5f
Source dataset
uspto-grants-2009_01
Patent number
US07476679B2

Reaction notes

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