Sodium Carbonate → 8-chloro-7-methoxy-3,4-dihydroisoquinolin-1(2H)-one

HRID 577473Notes

Reaction equation

HRID 577473 reaction equation
[CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([CH2:7][CH2:8][NH:9][C:10]2=[O:13])=[CH:5][CH:4]=1.C1C(=O)N([Cl:21])C(=O)C1.C([O-])([O-])=O.[Na+].[Na+]>OS(O)(=O)=O>[Cl:21][C:12]1[C:3]([O:2][CH3:1])=[CH:4][CH:5]=[C:6]2[C:11]=1[C:10](=[O:13])[NH:9][CH2:8][CH2:7]2

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 31398ChlorosuccinimideHCID 135216727-Methoxy-3,4-dihydroisoquinolin-1(2H)-one

Product 1

HCID 867237008-chloro-7-methoxy-3,4-dihydroisoquinolin-1(2H)-oneYield 50%

Reagents, catalysts & solvents 1

HCID 1118Sulfuric AcidSolvent

Procedure

To a mixture of 7-methoxy-3,4-dihydroisoquinolin-1(2H)-one (1c, 13.0 g, 73.9 mmol) in conc. H2SO4 (120 mL) was added portionwise NCS (10.4 g, 77.6 mmol) at 0° C. The reaction mixture was warmed to room temperature and stirred overnight. The reaction mixture was poured onto ice-water (200 mL). The solution was basified with Na2CO3 (s) to pH 8. The reaction mixture was extracted with EtOAc (2×200 mL). The combined organic layers were washed with brine (300 mL), dried over Na2SO4 and concentrated under vacuum. The residue was purified by column chromatography (petroleum ether/EtOAc, 1:1) to give 8-chloro-7-methoxy-3,4-dihydroisoquinolin-1(2H)-one (1d, 7.8 g, 50%) as a yellow solid.

Workup

  1. additionThe reaction mixture was poured onto ice-water (200 mL)
  2. extractionThe reaction mixture was extracted with EtOAc (2×200 mL)
  3. washThe combined organic layers were washed with brine (300 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under vacuum
  6. customThe residue was purified by column chromatography (petroleum ether/EtOAc, 1:1)

Sources & evidence

ORD record
ord-14b8e4fb7a914a7ba9e53366d6705793
Source dataset
uspto-grants-2015_05
Patent number
US09040515B2

Reaction notes

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