Water → HCID 22243415, compound

HRID 890958Notes

Reaction equation

HRID 890958 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[N:7][C:6]([C:12]([O:14]C)=[O:13])=[CH:5]2.[OH-].[K+].O>CCO>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[N:7][C:6]([C:12]([OH:14])=[O:13])=[CH:5]2

Participants

5

Reactant 3

HCID 962WaterHCID 14797Potassium HydroxideHCID 22243214HCID 22243214, compound

Product 1

HCID 22243415HCID 22243415, compoundYield 13.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

Methyl 6-chloro-isoquinoline3-carboxylate (0.80 g, 3.6 mmol) is suspended in 95% EtOH (35 mL). KOH (0.61 g, 10.9 mmol) is added, and the reaction is heated to 80° C. When a white precipitate begins to form, 10 mL of H2O is added and all solid is redissolved. After heating for 1 hour, the reaction is cooled to rt and a white precipitate forms. The precipitate (identified as the K+ salt) is collected by vacuum filtration. The filtrate is acidified with concentrated HCl until the pH is between 4 and 5. The filtrate is loaded directly onto a column of AGW-×2 resin (H+ form) and the column is rinsed with MeOH. The product is eluted with a solution of 5% TEA in MeOH. This solution is concentrated, evaporated from MeCN three times, and the resulting solid is recrystallized from EtOH/H2O. This material is purified by preparative achiral HPLC to yield 0.10 g (13%) of 6-chloroisoquinoline-3-carboxylic acid. HRMS (FAB) calculated for C10H6ClNO2+H+: 208.0165, found 208.0164.

Workup

  1. customto form
  2. dissolutionall solid is redissolved
  3. temperatureAfter heating for 1 hour
  4. temperaturethe reaction is cooled to rt
  5. filtrationis collected by vacuum filtration
  6. washthe column is rinsed with MeOH
  7. washThe product is eluted with a solution of 5% TEA in MeOH
  8. concentrationThis solution is concentrated
  9. customevaporated from MeCN three times
  10. customthe resulting solid is recrystallized from EtOH/H2O
  11. customThis material is purified by preparative achiral HPLC

Sources & evidence

ORD record
ord-5428cdfbbf3e42218c1c29398932b076
Source dataset
uspto-grants-2006_02
Patent number
US07001900B2

Reaction notes

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