4-(Trifluoromethylthio)benzyl bromide → 5-({4-[(Trifluoromethyl)sulphanyl]benzyl}oxy)-3,4-dihydroisoquinolin-1(2H)-one

HRID 705049Notes

Reaction equation

HRID 705049 reaction equation
[OH:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][NH:6][C:7]2=[O:12].Br[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([S:21][C:22]([F:25])([F:24])[F:23])=[CH:17][CH:16]=1>C(O)C>[F:23][C:22]([S:21][C:18]1[CH:19]=[CH:20][C:15]([CH2:14][O:1][C:2]2[CH:11]=[CH:10][CH:9]=[C:8]3[C:3]=2[CH2:4][CH2:5][NH:6][C:7]3=[O:12])=[CH:16][CH:17]=1)([F:25])[F:24]

Participants

4

Reactant 2

HCID 27778824-(Trifluoromethylthio)benzyl bromideHCID 132366635-Hydroxy-1,2,3,4-tetrahydroisoquinolin-1-one

Product 1

HCID 711865375-({4-[(Trifluoromethyl)sulphanyl]benzyl}oxy)-3,4-dihydroisoquinolin-1(2H)-one

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

166 mg (1.017 mmol) of 5-hydroxy-3,4-dihydroisoquinolin-1(2H)-one, 289 mg (1.068 mmol) of 1-(bromomethyl)-4-[(trifluoromethyl)sulphanyl]benzene and 365 mg (2.645 mmol) were suspended in 3 ml of ethanol and stirred under reflux for 6 h. After cooling, the insoluble constituents were filtered off and the solvent was removed under reduced pressure. The residue was dissolved in chloroform and water. The phases were separated, the organic phase was dried over sodium sulphate and the solvent was removed under reduced pressure. The crude product was purified by chromatography (ethyl acetate:n-heptane 2:1). This gave 200 mg (54% of theory) of the desired 5-({4-[(trifluoromethyl)sulphanyl]benzyl}oxy)-3,4-dihydroisoquinolin-1(2H)-one. 1H-NMR (400 MHz, d6-DMSO δ, ppm) 7.89 (br. s, 1H), 7.52-7.44 (m, 4H), 7.28 (t, 1H), 7.22 (d, 1H), 5.16 (s, 2H), 3.33 (dt, 2H), 2.84 (t, 2H).

Workup

  1. temperatureunder reflux for 6 h
  2. temperatureAfter cooling
  3. filtrationthe insoluble constituents were filtered off
  4. customthe solvent was removed under reduced pressure
  5. dissolutionThe residue was dissolved in chloroform
  6. customThe phases were separated
  7. dry with materialthe organic phase was dried over sodium sulphate
  8. customthe solvent was removed under reduced pressure
  9. customThe crude product was purified by chromatography (ethyl acetate:n-heptane 2:1)

Sources & evidence

ORD record
ord-907f808b185b4e4ab0be6288ee03dd8a
Source dataset
uspto-grants-2015_11
Patent number
US09173395B2

Reaction notes

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