Citric Acid → HCID 178515330, compound

HRID 1881759Notes

Reaction equation

HRID 1881759 reaction equation
[S:1]=[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH2:5][C:4](=[O:12])[NH:3]1.C([O-])([O-])=O.[K+].[K+].Br[CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[Cl:27].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CCO>[Cl:27][C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=1[CH2:20][S:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[C:4]([OH:12])[N:3]=1

Participants

6

Reactant 4

HCID 311Citric AcidHCID 11430Potassium CarbonateHCID 11905alpha-Bromo-o-chlorotolueneHCID 2752457HCID 2752457, compound

Product 1

HCID 178515330HCID 178515330, compoundYield 84.8%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a 50 mL round bottom flask was added 1-thioxo-1,4-dihydro-2H-isoquinolin-3-one (0.8 g, 4.51 mmol), K2CO3 (1.9 g, 13.5 mmol), and absolute EtOH (15 mL) followed by 1-(bromomethyl)-2-chlorobenzene (0.88 g, 4.29 mmol). Upon completion of addition, the reaction mixture was stirred for 18 h. At the conclusion of this period, the reaction mixture was acidified with a solution of citric acid (100 mL, 10% w/v), extracted with EtOAc (100 mL), washed with brine (75 mL) and then dried over Na2SO4. The solvent was removed under vacuum to yield a residue. The residue was purified via silica gel chromatography (20% EtOAc:Hex) to yield the title compound as a pale yellow solid (1.1 g, 3.64 mmol, 81%). 1H NMR (400 MHz, DMSO-d6): δ ppm 8.05 (d, J=8.35 Hz, 1H), 7.59-7.64 (m, 1H), 7.50-7.57 (m, 2H), 7.37-7.42 (m, 1H), 7.31 (ddd, J=8.46, 6.92, 1.32 Hz, 1H), 7.16-7.23 (m, 2H), 6.71 (s, 1H), 5.92 (br. s., 1H), 4.67 (s, 2H). LC/MS m/z 302 [M+H].

Workup

  1. additionUpon completion of addition
  2. extractionextracted with EtOAc (100 mL)
  3. washwashed with brine (75 mL)
  4. dry with materialdried over Na2SO4
  5. customThe solvent was removed under vacuum
  6. customto yield a residue
  7. customThe residue was purified via silica gel chromatography (20% EtOAc:Hex)

Sources & evidence

ORD record
ord-d3d18352742746ee80bd4b90bf76857e
Source dataset
uspto-grants-2012_11
Patent number
US08318941B2

Reaction notes

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