Trifluoroacetic acid → 4-(1,2,3,4-Tetrahydro-isoquinolin-6-yloxy)-benzamide

HRID 492539Notes

Reaction equation

HRID 492539 reaction equation
C(OC([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([O:18][C:19]3[CH:24]=[CH:23][C:22]([C:25](=[O:27])[NH2:26])=[CH:21][CH:20]=3)[CH:14]=2)[CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O.C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl>[CH2:9]1[C:10]2[C:15](=[CH:14][C:13]([O:18][C:19]3[CH:24]=[CH:23][C:22]([C:25]([NH2:26])=[O:27])=[CH:21][CH:20]=3)=[CH:12][CH:11]=2)[CH2:16][CH2:17][NH:8]1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 597299826-(4-carbamoyl-phenoxy)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester

Product 1

HCID 597301424-(1,2,3,4-Tetrahydro-isoquinolin-6-yloxy)-benzamideYield 71.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Combine 6-(4-carbamoyl-phenoxy)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester (4.0 g, 10.83 mmol), CH2Cl2 (100 mL), and TFA (25 mL) at room temperature. Stir for 24 hours, followed by the addition of 1.0 M K2CO3 (aq), and extract the product out of the aqueous layer with several washings of ethyl acetate/THF. Concentrate the organic phase under reduced pressure and add to 2, 10 g SCX Columns pre-treated with 5% AcOH/MeOH. After several washings of the SCX Columns with MeOH, elute with 1.0 N NH3-MeOH solution to afford 2.08 g, 7.7 mmol (71% yield) of the title compound as a white foam: 1H NMR (500 MHz, DMSO-d6); 2.9-3.1 (2H, m), 3.10-3.25 (1H, m), 3.3-3.5 (2H, m), 4.1-4.3 (2H, m), 7.0-7.2 (3H, m), 7.2-7.4 (1H, m), 7.4-7.6 (1H, m), 8.0-8.1 (1H, m), 8.2-8.4 (1H, m), 8.5-8.65 (1H, m), 9.2-9.4 (2H, m); MS m/z 269 (M+1).

Workup

  1. customat room temperature
  2. extractionextract the product out of the aqueous layer with several washings of ethyl acetate/THF
  3. concentrationConcentrate the organic phase under reduced pressure
  4. additionadd to 2, 10 g SCX Columns
  5. additionpre-treated with 5% AcOH/MeOH
  6. washAfter several washings of the SCX Columns with MeOH, elute with 1.0 N NH3-MeOH solution

Sources & evidence

ORD record
ord-0aa05eb6701f4c1baaf97d5fd551cb50
Source dataset
uspto-grants-2009_05
Patent number
US07531557B2

Reaction notes

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