Hydrochloric Acid → 3-Chloro-7-methoxyisoquinoline

HRID 1472724Notes

Reaction equation

HRID 1472724 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH3:13])[CH:10]=2)[CH:5]=[C:4]([Cl:14])[N:3]=1.Cl.[Sn].[NH4+].[OH-]>C(O)(=O)C>[Cl:14][C:4]1[N:3]=[CH:2][C:11]2[C:6]([CH:5]=1)=[CH:7][CH:8]=[C:9]([O:12][CH3:13])[CH:10]=2

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14923Ammonium HydroxideHCID 5352426Tin atomHCID 716915371,3-Dichloro-7-methoxyisoquinoline

Product 1

HCID 534255653-Chloro-7-methoxyisoquinolineYield 21%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
60 °C

Procedure

1,3-dichloro-7-methoxyisoquinoline (1.14 g, 5.00 mmol) was suspended in glacial acetic acid (6 mL) and concentrated HCl (2 mL), then treated with tin powder (1.77 g, 15.0 mmol) and stirred at 60° C. for 3 hours. The resulting mixture was basified to pH=9 with concentrated NH4OH and then extracted with ethyl acetate (10 mL×3). The combined organic layer was washed with saturated NaHCO3 solution (20 mL), dried over Na2SO4 and concentrated in vacuo, followed by silica gel column (EtOAc/PE=20:1) to give Intermediate 12 (200 mg, yield 21%) as a solid. 1H NMR (DMSO 300 MHz): δ 9.00 (s, 1H), 7.94 (s, 1H), 8.87 (d, J=9.0 Hz, 1H), 7.53 (d, J=2.7 Hz, 1H), 7.46 (dd, J=9.0, 2.7 Hz, 1H), 3.89 (s, 3H).

Workup

  1. extractionextracted with ethyl acetate (10 mL×3)
  2. washThe combined organic layer was washed with saturated NaHCO3 solution (20 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d086a85030b74595b91ba4057df2c57e
Source dataset
uspto-grants-2015_04
Patent number
US09012646B2

Reaction notes

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