Hydrochloric Acid → 2-(Isoquinolin-4-yl)acetic acid hydrochloride

HRID 900705Notes

Reaction equation

HRID 900705 reaction equation
C([BH-](CC)CC)C.[Na+].[CH:9]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH:12]=[CH:11][N:10]=1.[C:19]([O:23]CC)(=[O:22])[CH:20]=O.[OH-].[Na+].OO.[ClH:30]>C1COCC1.C1(C)C=CC=CC=1>[ClH:30].[CH:9]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:12]([CH2:20][C:19]([OH:23])=[O:22])=[CH:11][N:10]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 784Hydrogen PeroxideHCID 8405IsoquinolineHCID 14798Sodium HydroxideHCID 70211Ethyl oxoacetateHCID 5129078Sodium triethylboranuide

Product 1

HCID 692001992-(Isoquinolin-4-yl)acetic acid hydrochloride

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of sodium triethylborohydride (1M THF, 12.7 ml, 12.7 mmol) is added dropwise to a solution of isoquinoline (1.64 g, 12.7 mmol) in THF (25 ml). The reaction is stirred at room temperature for 1 hour, prior to dropwise addition of a solution of ethyl glyoxalate (1.43 g, 13.9 mmol) in toluene (previously heated at 110° C. for 1.5 hours). After a further 4 hours at room temperature, the reaction is cooled to 0° C. and sodium hydroxide (0.5 M aqueous solution, 25.4 ml) followed by hydrogen peroxide (30% aqueous solution, 12.7 ml) is added, followed by stirring for 2 hours. The reaction is acidified with 1N HCl, washed with ethyl acetate three times, the aqueous phase is reduced in volume by evaporation and refrigerated overnight. The resultant precipitate is collected by filtration and dried to afford isoquinolin-4-yl-acetic acid hydrochloride salt, MH+ 188.

Workup

  1. temperaturepreviously heated at 110° C. for 1.5 hours)
  2. waitAfter a further 4 hours at room temperature
  3. temperaturethe reaction is cooled to 0° C.
  4. additionis added
  5. stirringby stirring for 2 hours
  6. washwashed with ethyl acetate three times
  7. customthe aqueous phase is reduced in volume by evaporation and refrigerated overnight
  8. filtrationThe resultant precipitate is collected by filtration
  9. customdried

Sources & evidence

ORD record
ord-2f729cea6b9d4257886ae4988660cb8a
Source dataset
uspto-grants-2008_04
Patent number
US07361661B2

Reaction notes

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