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

HRID 131023Notes

Reaction equation

HRID 131023 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. After the reaction stirred for 24 hours followed by the addition of 1M K2CO3 (aq), 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, the elute the product using 1N 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); 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, the elute the product

Sources & evidence

ORD record
ord-cbcafa2ff8c64d00b0ad9b4c17e41ff2
Source dataset
uspto-grants-2008_06
Patent number
US07381719B2

Reaction notes

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