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

HRID 1453972ノート

反応式

HRID 1453972 の反応式
[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

参加物

4

反応物 2

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-a6487c323f2b4c74b1a1758aa5420f5f
出典データセット
uspto-grants-2009_01
特許番号
US07476679B2

反応ノート

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