Acetic Acid → HCID 22226520, compound

HRID 1745810Notes

Reaction equation

HRID 1745810 reaction equation
[BH4-].[Na+].[Br:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[CH:10]=[N:9][CH:8]=[CH:7]2.[C:14](O)(=[O:16])[CH3:15]>C(OC(=O)C)(=O)C>[Br:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[CH2:10][N:9]([C:14](=[O:16])[CH3:15])[CH:8]=[CH:7]2

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 3136816-BromoisoquinolineHCID 4311764Sodium borohydride

Product 1

HCID 22226520HCID 22226520, compound

Reagents, catalysts & solvents 1

HCID 7918Acetic AnhydrideSolvent

Conditions

Temperature
60 °C

Procedure

Sodium borohydride (1.12 g, 29.6 mmol) is added portionwise to a cooled (0° C.) solution of 6-bromoisoquinoline [J Chem Soc Perkin Trans 2, 1998, 437] (1.544 g, 7.42 mmol) in acetic acid (10 ml) and acetic anhydride (3 ml). After heating at 60° C. for 4 hours, the mixture is cooled, evaporated and diluted with water. After adjustment to pH10 with potassium carbonate and extraction with ethyl acetate, the combined organic phases are washed twice with 0.5N HCl and brine, then dried over sodium sulphate. Evaporation affords 1-(6-bromo-1H-isoquinolin-2-yl)-ethanone, MH+ 253. Glyoxylic acid (0.812 g, 8.80 mmol) is added to mixture of 1-(6-bromo-1H-isoquinolin-2-yl)-ethanone (1.50 g, 5.90 mmol) in 6N HCl (20 ml). The reaction is heated at 100° C. for 2 hours, cooled to RT and washed with ethyl acetate. After evaporation, the residue is taken into methanol (20 ml), concentrated sulphuric acid (10 drops) is added and the mixture heated at reflux for 14 hours. After partial evaporation of the solvent, the resultant solid is collected by filtration, washed with methanol and dried to afford (6-bromo-isoquinolin-4-yl)-acetic acid methyl ester cooled (0° C.) solution of (6-bromo-isoquinolin-4-yl)-acetic acid methyl ester (50 mg, 0.18 mmol) in 3:1 THF-water (3 ml). After 1 hour the solvent is evaporated to afford (6-bromo-isoquinolin-4-yl)-acetic acid lithium salt, MH+ 266.

Workup

  1. temperaturethe mixture is cooled
  2. customevaporated
  3. additiondiluted with water
  4. extractionAfter adjustment to pH10 with potassium carbonate and extraction with ethyl acetate
  5. washthe combined organic phases are washed twice with 0.5N HCl and brine
  6. dry with materialdried over sodium sulphate
  7. customEvaporation

Sources & evidence

ORD record
ord-71fa93e1713e40ec9897e9ffcb49a162
Source dataset
uspto-grants-2006_03
Patent number
US07019136B2

Reaction notes

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