Sulfuric Acid → (6-Chloro-3-methyl-isoquinolin-5-yl)-acetic acid methyl ester

HRID 505215Notes

Reaction equation

HRID 505215 reaction equation
[Cl:1][C:2]1[C:3]([CH2:13][C:14](Cl)(Cl)Cl)=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[N:7][C:6]([CH3:12])=[CH:5]2.C[O-:19].[Na+].OS(O)(=O)=O.[C:26]([O-])(O)=[O:27].[Na+]>CO>[CH3:26][O:27][C:14](=[O:19])[CH2:13][C:3]1[C:2]([Cl:1])=[CH:11][CH:10]=[C:9]2[C:4]=1[CH:5]=[C:6]([CH3:12])[N:7]=[CH:8]2

Participants

6

Reactant 4

HCID 1118Sulfuric AcidHCID 516892Sodium BicarbonateHCID 10942334Sodium MethoxideHCID 668811066-Chloro-3-methyl-5-(2,2,2-trichloroethyl)isoquinoline

Product 1

HCID 66882229(6-Chloro-3-methyl-isoquinolin-5-yl)-acetic acid methyl esterYield 70%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
70 °C

Procedure

To a solution of 6-chloro-3-methyl-5-(2,2,2-trichloro-ethyl)isoquinoline (3.3 g, 10.7 mmol) in anhydrous methanol (64 mL) was added a 30% solution of NaOMe in methanol (9.6 mL) under an argon atmosphere. The resulting brown solution was heated for 3 h at 70° C. After cooling to 0° C., concentrated H2SO4 (5.7 mL) was carefully added and the resulting reaction mixture was heated for 1 h at 70° C. After cooling the reaction mixture was rendered basic (pH=9) with a saturated aqueous NaHCO3 solution and extracted three times with diethyl ether. The combined organic layers were dried over Na2SO4, filtered and concentrated at reduced pressure to afford a brown solid. Purification by flash column chromatography (silica gel, cyclohexane/ethyl actetate 70:30) afforded the title compound as a brown powder (1.91 g, 7.63 mmol, 70%). MS (ES+): 250 (M(C13H1235ClNO2)+H)+.

Workup

  1. temperatureAfter cooling to 0° C.
  2. customthe resulting reaction mixture
  3. temperaturewas heated for 1 h at 70° C
  4. temperatureAfter cooling the reaction mixture
  5. extractionextracted three times with diethyl ether
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated at reduced pressure
  9. customto afford a brown solid
  10. customPurification by flash column chromatography (silica gel, cyclohexane/ethyl actetate 70:30)

Sources & evidence

ORD record
ord-f392a6a43a104a17824a2e09aee01e61
Source dataset
uspto-grants-2010_08
Patent number
US07781438B2

Reaction notes

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