1,2-Dichloroethane → N-(3-Phenylpropyl)-6-amino-4a-(3-methoxyphenyl)-8a-methyloctahydro-isoquinoline Phthalimide

HRID 1453974Notes

Reaction equation

HRID 1453974 reaction equation
[CH:1](=O)[CH2:2][CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[C:11]1(=[O:21])[NH:15][C:14](=[O:16])[C:13]2=[CH:17][CH:18]=[CH:19][CH:20]=[C:12]12.N[CH:23]1C2(C)[C:27]([C:34]3[CH:39]=[CH:38][CH:37]=[C:36]([O:40][CH3:41])[CH:35]=3)([CH2:28][CH2:29][CH2:30][CH2:31]2)[CH2:26][CH2:25][NH:24]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].Cl[CH2:57][CH2:58]Cl>>[C:11]1(=[O:21])[NH:15][C:14](=[O:16])[C:13]2=[CH:17][CH:18]=[CH:19][CH:20]=[C:12]12.[C:4]1([CH2:3][CH2:2][CH2:1][N:24]2[CH2:25][CH2:26][C:27]3([C:34]4[CH:39]=[CH:38][CH:37]=[C:36]([O:40][CH3:41])[CH:35]=4)[C:57]([CH3:58])([CH2:31][CH2:30][CH:29]([NH2:15])[CH2:28]3)[CH2:23]2)[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

5

Reactant 4

HCID 111,2-DichloroethaneHCID 7707BenzenepropanalHCID 5049666Sodium triacetoxyborohydrideHCID 68828071Amino-4a-(3-methoxyphenyl)-8a-methyloctahydroisoquinoline Phthalimide

Product 1

HCID 68827564N-(3-Phenylpropyl)-6-amino-4a-(3-methoxyphenyl)-8a-methyloctahydro-isoquinoline PhthalimideYield 87%

Procedure

Hydrocinnamaldehyde (0.65 mL, 0.0049 mol) and compound 22 (2.00 g, 0.0049 mol) were mixed in anhydrous 1,2-dichloroethane (50 mL) and then treated with sodium triacetoxyborohydride (1.57 g, 0.0074 mol). The reaction mixture remains cloudy throughout the reaction. The mixture was stirred at room temperature under N2 atmosphere for 3 h. Reaction was monitored by TLC (20% EtOAc/hexanes; neutral Al2O3 Brockman activity II-III). After completion, the reaction mixture was quenched by adding saturated aqueous NaHCO3, and the product was extracted with EtOAc (3×50 mL). The combined EtOAc extract were dried (MgSO4), and the solvent was removed under reduced pressure to give crude product. The crude product was purified by flash chromatography (10% EtOAc/hexanes on neutral Al2O3 Brockman activity II-III) to afford 2.25 g (87%) of 23 as a white shiny solid. The sample used for X-ray analysis was recrystallized from a hexane and methylene chloride mixture: mp 136-138° C.; LCMS (ESI): m/z 523.7 (M+H)+; 1H NMR (CDCl3, 300 MHz) δ 7.79-7.82 [m, 2H], 7.68-7.71 [m, 2H], 7.18-7.32 [m, 8H], 6.76-6.81 [m, 1H], 4.81 [m, 1H], 3.85 [s, 3H], 3.31 [t, J=12 Hz, 1H], 2.94 [d, J=12 Hz, 1H], 2.80 [d, J=9 Hz, 1H], 2.67-2.73 [m, 3H], 2.34-2.53 [m, 4H], 2.25 [d, J=12 Hz, 1H], 1.78-1.94 [m, 3H], 1.51-1.62 [m, 2H], 1.49 [d, J=12 Hz, 1H], 1.31-1.37 [m, 1H], 1.26 [s, 3H]; 13C NMR (CDCl3, 300 MHz) δ 170.4, 160.9, 150.3, 144.5, 135.7, 134.0, 130.4, 130.3, 130.2, 127.6, 124.9, 123.5, 117.6, 112.6, 90.0, 63.6, 59.9, 57.2, 52.9, 49.5, 46.2, 38.6, 38.5, 37.3, 35.7, 35.6, 31.0, 28.3, 25.9. Anal. (C34H38N2O3) C, H, N.

Workup

  1. customThe reaction mixture remains cloudy throughout the reaction
  2. customReaction
  3. customAfter completion, the reaction mixture was quenched
  4. additionby adding saturated aqueous NaHCO3
  5. extractionthe product was extracted with EtOAc (3×50 mL)
  6. extractionThe combined EtOAc extract
  7. dry with materialwere dried (MgSO4)
  8. customthe solvent was removed under reduced pressure
  9. customto give crude product
  10. customThe crude product was purified by flash chromatography (10% EtOAc/hexanes on neutral Al2O3 Brockman activity II-III)

Sources & evidence

ORD record
ord-e0aa1dd06b784f1aa83ae85d4a004541
Source dataset
uspto-grants-2009_01
Patent number
US07476679B2

Reaction notes

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