Methanol → N-propyl-8,9-dihydroxy-1,2,3,11b-tetrahydrochromeno [4,3,2-de]isoquinoline

HRID 895405Notes

Reaction equation

HRID 895405 reaction equation
[CH2:1]([N:4]1[CH2:13][CH:12]2[C:14]3[CH:15]=[CH:16][C:17]([O:23]C)=[C:18]([O:21]C)[C:19]=3[O:20][C:10]3[C:11]2=[C:6]([CH:7]=[CH:8][CH:9]=3)[CH2:5]1)[CH2:2][CH3:3].B(Br)(Br)Br.CO>ClCCl>[CH2:1]([N:4]1[CH2:13][CH:12]2[C:14]3[CH:15]=[CH:16][C:17]([OH:23])=[C:18]([OH:21])[C:19]=3[O:20][C:10]3[C:11]2=[C:6]([CH:7]=[CH:8][CH:9]=3)[CH2:5]1)[CH2:2][CH3:3]

Participants

5

Reactant 3

HCID 887MethanolHCID 25134Boron tribromide2×HCID 22380771N-propyl-8,9-dimethoxy-1,2,3,11b-tetrahydrochromeno [4,3,2-de]isoquinoline

Product 1

HCID 10469910N-propyl-8,9-dihydroxy-1,2,3,11b-tetrahydrochromeno [4,3,2-de]isoquinoline

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

The N-propyl amine 12a (0.90 g; 2.8 mmol) was dissolved in 200 ml of dichloromethane and cooled to −78° C. In a separate 250 ml round bottom flask, 125 ml of dry dichloromethane was cooled to −78° C., and 1.4 ml (14.8 mmol) of BBr3 was added via syringe. The BBr3 solution was transferred using a cannula to the flask containing the starting material. The solution was stirred overnight, while the reaction slowly warmed to room temperature. After recooling the solution to −78° C., 50 ml of methanol was slowly added to quench the reaction. The reaction was then concentrated to dryness. Methanol was added and the solution was concentrated. This process was repeated three times. The resulting tan solid was suspended in hot isopropyl alcohol. Slowly cooling to room temperature resulted in a fine yellow precipitate. The solid was collected by filtration (0.660 g; 63%): mp 259-264° C. dec; 1H NMR: (300 MHz, CDCl3): 7.16 (t, 1H, J=9 Hz); 6.97 (d, 1H, J=12 Hz); 6.83 (d, 1H, J=9 Hz); 6.55 (d, 1H, J=9 Hz); 6.46 (d, 1H, J=9 Hz); 4.45 (d, 1H, J=15 Hz); 4.10 (m, 3H); 3.17 (q, 2H, J=6 Hz); 3.04 (t, 1H, J=9 Hz); 1.73 (q, 2H, J=9 Hz); 0.90 (t, 3H, J=6 Hz). Anal. Calc'd. for C18H20BrNO3: C, 57.16; H, 5.33; N, 3.70. Found: C, 56.78; H, 5.26; N, 3.65.

Workup

  1. additioncontaining the starting material
  2. temperatureslowly warmed to room temperature
  3. customto −78° C.
  4. customto quench
  5. customthe reaction
  6. concentrationThe reaction was then concentrated to dryness
  7. additionMethanol was added
  8. concentrationthe solution was concentrated
  9. temperatureSlowly cooling to room temperature
  10. customresulted in a fine yellow precipitate
  11. filtrationThe solid was collected by filtration (0.660 g; 63%)

Sources & evidence

ORD record
ord-3c589de7e0f74f69865e95c465f8f6fa
Source dataset
uspto-grants-2005_07
Patent number
US06916823B2

Reaction notes

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