Acetic Acid → 2-(2-(4-(2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)phenyl)-2H-tetrazol-5-yl)-4,5-dimethoxyaniline(WXC04283)

HRID 1430613Notes

Reaction equation

HRID 1430613 reaction equation
C(O)(=O)C.[CH3:5][O:6][C:7]1[C:12]([O:13][CH3:14])=[CH:11][C:10]([C:15]2[N:16]=[N:17][N:18]([C:20]3[CH:41]=[CH:40][C:23]([CH2:24][CH2:25][N:26]4[CH2:35][CH2:34][C:33]5[C:28](=[CH:29][C:30]([O:38][CH3:39])=[C:31]([O:36][CH3:37])[CH:32]=5)[CH2:27]4)=[CH:22][CH:21]=3)[N:19]=2)=[C:9]([N+:42]([O-])=O)[CH:8]=1.C(Cl)(Cl)Cl.CO.C(Cl)(Cl)Cl>[Fe].O>[CH3:37][O:36][C:31]1[CH:32]=[C:33]2[C:28](=[CH:29][C:30]=1[O:38][CH3:39])[CH2:27][N:26]([CH2:25][CH2:24][C:23]1[CH:40]=[CH:41][C:20]([N:18]3[N:17]=[N:16][C:15]([C:10]4[CH:11]=[C:12]([O:13][CH3:14])[C:7]([O:6][CH3:5])=[CH:8][C:9]=4[NH2:42])=[N:19]3)=[CH:21][CH:22]=1)[CH2:35][CH2:34]2

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 6212ChloroformHCID 21584188Chloroform methanolHCID 69033270HCID 69033270, compound

Product 1

HCID 675270732-(2-(4-(2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)phenyl)-2H-tetrazol-5-yl)-4,5-dimethoxyaniline(WXC04283)Yield 87%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

Iron (433 g, 7.76 mol) and 5.4 L of 50% aqueous acetic acid were added to a reactor, and stirred for 1 hour at 80° C. 2-(4-(5-(4,5-dimethoxy-2-nitrophenyl)-2H-tetrazol-2-yl)phenethyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (1.06 kg, 1.94 mol) obtained in Step 4 was slowly added thereto for two hours, followed by stirring for 1 hour. After checking completion of the reaction by thin layer chromatography (eluent: chloroform/methanol=15/1), the reactor was cooled to room temperature. 5.3 L of chloroform and 2.4 L of water were added thereto and the resulting mixture was filtered through a Celite pad. The organic layer was collected, 6.6 L of saturated sodium bicarbonate solution was slowly added thereto with stirring. The organic layer was collected, and the aqueous layer was further extracted using 1.25 L of chloroform. The resulting organic layer was dried over magnesium sulfate, and then distilled under reduced pressure to remove the solvent. The residue was mixed with 10.6 L of methanol, followed by stirring. The resulting mixture was filtered, and dried with hot air at 40° C. in an oven to obtain the title compound (0.87 kg, 87%).

Workup

  1. waitfor two hours
  2. stirringby stirring for 1 hour
  3. temperaturethe reactor was cooled to room temperature
  4. filtrationthe resulting mixture was filtered through a Celite pad
  5. customThe organic layer was collected
  6. addition6.6 L of saturated sodium bicarbonate solution was slowly added
  7. stirringwith stirring
  8. customThe organic layer was collected
  9. extractionthe aqueous layer was further extracted
  10. dry with materialThe resulting organic layer was dried over magnesium sulfate
  11. distillationdistilled under reduced pressure
  12. customto remove the solvent
  13. additionThe residue was mixed with 10.6 L of methanol
  14. stirringby stirring
  15. filtrationThe resulting mixture was filtered
  16. customdried with hot air at 40° C. in an oven

Sources & evidence

ORD record
ord-5e469455ca10419cb7d8dd2ec9ec48aa
Source dataset
uspto-grants-2015_01
Patent number
US08940908B2

Reaction notes

Loading…