Ammonium Chloride → 2-Benzyl-5-bromo-3,4-dihydroisoquinolin-1(2H)-one

HRID 387633Notes

Reaction equation

HRID 387633 reaction equation
[CH2:1]([N:8]([CH2:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[Br:21])[C:9](=O)[O:10]C)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.[Cl-].[NH4+]>ClCCl.CN(C)C1C=CN=CC=1>[CH2:1]([N:8]1[CH2:13][CH2:14][C:15]2[C:20](=[CH:19][CH:18]=[CH:17][C:16]=2[Br:21])[C:9]1=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 67749Trifluoromethanesulfonic anhydrideHCID 68470524Methyl benzyl[2-(2-bromophenyl)ethyl]carbamate

Product 1

HCID 218654522-Benzyl-5-bromo-3,4-dihydroisoquinolin-1(2H)-oneYield 48.5%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

0.5 g of methyl benzyl[2-(2-bromophenyl)ethyl]carbamate is dissolved under an inert atmosphere in 20 cm3 of dichloromethane at a temperature close to 20° C. 0.526 g of N,N-dimethylpyridin-4-amine is added, then the reaction mixture is cooled to a temperature close to 0° C. 1.2 cm3 of trifluoromethanesulfonic anhydride is introduced dropwise. The suspension obtained is stirred for 15 min at a temperature close to 0° C., then for 4 h 30 min while allowing it to gradually climb back up to a temperature close to 20° C. Dichloromethane is added to the reaction mixture and also a saturated aqueous solution of ammonium chloride. The aqueous phase is extracted with dichloromethane. The organic phases are combined, dried over magnesium sulfate then concentrated using a rotary evaporator under reduced pressure (5 kPa). The crude product obtained (1 g) is purified by flash chromatography over silica (column: 90 g; particle size: 15-40 μm; eluent: 100% dichloromethane to 95% dichloromethane/5% ethyl acetate gradient). After concentrating the fractions under reduced pressure, 0.22 g of 2-benzyl-5-bromo-3,4-dihydroisoquinolin-1(2 H)-one is obtained.

Workup

  1. customclose to 20° C
  2. temperaturethe reaction mixture is cooled to a temperature
  3. customclose to 0° C
  4. customThe suspension obtained
  5. customclose to 0° C.
  6. waitfor 4 h 30 min while allowing
  7. customclose to 20° C
  8. extractionThe aqueous phase is extracted with dichloromethane
  9. dry with materialdried over magnesium sulfate
  10. concentrationthen concentrated
  11. customa rotary evaporator under reduced pressure (5 kPa)
  12. customThe crude product obtained (1 g)
  13. customis purified by flash chromatography over silica (column: 90 g; particle size: 15-40 μm; eluent: 100% dichloromethane to 95% dichloromethane/5% ethyl acetate gradient)
  14. concentrationAfter concentrating the fractions under reduced pressure

Sources & evidence

ORD record
ord-dea9b17847d7428a84d0ca366b3f81e9
Source dataset
uspto-grants-2013_02
Patent number
US08372864B2

Reaction notes

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