Hydrazine hydrate (1:1) → N-(3-Phenylpropyl)-6-amino-4a-(3-methoxyphenyl)-8a-methyloctahydroisoquinoline

HRID 1453975Notes

Reaction equation

HRID 1453975 reaction equation
C1(=O)NC(=O)C2=CC=CC=C12.[C:12]1([CH2:18][CH2:19][CH2:20][N:21]2[CH2:30][CH2:29][C:28]3([C:31]4[CH:36]=[CH:35][CH:34]=[C:33]([O:37][CH3:38])[CH:32]=4)[C:23]([CH3:40])([CH2:24][CH2:25][CH:26]([NH2:39])[CH2:27]3)[CH2:22]2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.O.NN>C(O)C>[C:12]1([CH2:18][CH2:19][CH2:20][N:21]2[CH2:30][CH2:29][C:28]3([C:31]4[CH:36]=[CH:35][CH:34]=[C:33]([O:37][CH3:38])[CH:32]=4)[C:23]([CH3:40])([CH2:24][CH2:25][CH:26]([NH2:39])[CH2:27]3)[CH2:22]2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 68827564N-(3-Phenylpropyl)-6-amino-4a-(3-methoxyphenyl)-8a-methyloctahydro-isoquinoline Phthalimide

Product 1

HCID 68827565N-(3-Phenylpropyl)-6-amino-4a-(3-methoxyphenyl)-8a-methyloctahydroisoquinolineYield 97.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Compound 23 (2.00 g, 0.0038 mol) and hydrazine hydrate (1.02 mL, 21.0 mmol) were dissolved in ethanol (100 mL) and refluxed overnight. The solution was then cooled, and the white precipitate was filtered and washed with cold ethanol. The solution was concentrated under reduced pressure and the crude material taken up in 3:1, CH2Cl2/THF (100 mL). The resulting white precipitate was filtered and washed with cold CH2Cl2 (50 mL). The combined organic layer was dried (Na2SO4) and concentrated under reduced pressure to yield crude product. The crude product was purified by flash chromatography (40% CMA 80 in CHCl3) to afford 1.45 g (97%) of 24 as a colorless oil: LCMS (APCI): m/z 393.8 (M+H)+; 1H NMR (CDCl3, 300 MHz) δ 7.14-7.30 [m, 8H], 6.70-6.74 [m, 1H], 3.86 [s, 3H], 3.05 [m, 1H], 2.77-2.79 [br m, 1H], 2.65 [ddd, J1=J2=9 Hz, J3=3 Hz, 2H], 2.58 [d, J=12 Hz, 1H], 2.26-2.36 [m, 4H], 2.04-2.12 [m, 3H], 1.68-1.81 [m, 4H], 1.44-1.50 [m, 4H], 1.32 [m, 1H], 1.21 [s, 3H]; 13C NMR (CDCl3, 300 MHz) δ 159.2, 150.3, 142.9, 128.9, 128.6, 128.5, 126.0, 121.8, 116.5, 110.0, 62.6, 58.2, 55.5, 51.3, 46.9, 44.5, 43.2, 36.7, 36.3, 34.0, 32.1, 29.2, 25.8.

Workup

  1. temperaturerefluxed overnight
  2. temperatureThe solution was then cooled
  3. filtrationthe white precipitate was filtered
  4. washwashed with cold ethanol
  5. concentrationThe solution was concentrated under reduced pressure
  6. filtrationThe resulting white precipitate was filtered
  7. washwashed with cold CH2Cl2 (50 mL)
  8. dry with materialThe combined organic layer was dried (Na2SO4)
  9. concentrationconcentrated under reduced pressure
  10. customto yield crude product
  11. customThe crude product was purified by flash chromatography (40% CMA 80 in CHCl3)

Sources & evidence

ORD record
ord-2320ff759af3459883e14787f0c65bb9
Source dataset
uspto-grants-2009_01
Patent number
US07476679B2

Reaction notes

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