Chloroform → 1,2,3,4-Tetrahydro-1-oxo-6-isoquinolinecarboxylic acid

HRID 389102Notes

Reaction equation

HRID 389102 reaction equation
[OH-:1].[K+].FC(F)(F)S(O[C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[C:15](=[O:19])[NH:14][CH2:13][CH2:12]2)(=O)=O.C(Cl)(Cl)Cl.CN1[C:31](=[O:32])CCC1>[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[O:19]=[C:15]1[C:16]2[C:11](=[CH:10][C:9]([C:31]([OH:32])=[O:1])=[CH:18][CH:17]=2)[CH2:12][CH2:13][NH:14]1

Participants

7

Reactant 4

HCID 6212ChloroformHCID 13387N-methyl-2-pyrrolidoneHCID 14797Potassium HydroxideHCID 534141981-Oxo-1,2,3,4-tetrahydroisoquinolin-6-YL trifluoromethanesulfonate

Product 1

HCID 582439051,2,3,4-Tetrahydro-1-oxo-6-isoquinolinecarboxylic acid

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
120 °C

Procedure

Zinc cyanide (744 mg), potassium hydroxide (470 mg) and tetrakis(triphenylphosphine)palladium (0) (1.82 g) were sequentially added to a solution of 1-oxo-1,2,3,4-tetrahydroisoquinolin-6-yl trifluoromethanesulfonate (1.55 g) in NMP (15 ml), followed by stirring at 120° C. for 3 hours. Chloroform was added to the reaction solution, the precipitated solid was separated by filtration, and the solvent of the filtrate was evaporated. The residue was purified by silica gel chromatography (hexane:ethyl acetate=100:0 to 0:100), and the solvent was evaporated under reduced pressure. Subsequently, ethylene glycol (10 ml) and 3M aqueous sodium hydroxide solution (30 ml) were added to the resulting residue, followed by stirring at 100° C. for 3 hours. After cooling to room temperature, water was added thereto, followed by extraction with diethylether. Concentrated hydrochloric acid was added to the aqueous layer, the pH was adjusted to 2 to 3, ethyl acetate was added for re-extraction, the organic layer was washed with saturated brine, and the solvent was evaporated under reduced pressure. Ethyl acetate was added, and the solid was precipitated, filtered and dried under vacuum to obtain, as a colorless solid, 1-oxo-1,2,3,4-tetrahydroisoquinoline-6-carboxylic acid (324 mg).

Workup

  1. customthe precipitated solid was separated by filtration
  2. customthe solvent of the filtrate was evaporated
  3. customThe residue was purified by silica gel chromatography (hexane:ethyl acetate=100:0 to 0:100)
  4. customthe solvent was evaporated under reduced pressure
  5. additionSubsequently, ethylene glycol (10 ml) and 3M aqueous sodium hydroxide solution (30 ml) were added to the resulting residue
  6. stirringby stirring at 100° C. for 3 hours
  7. temperatureAfter cooling to room temperature
  8. additionwater was added
  9. extractionfollowed by extraction with diethylether
  10. additionConcentrated hydrochloric acid was added to the aqueous layer
  11. additionwas added for re-extraction
  12. washthe organic layer was washed with saturated brine
  13. customthe solvent was evaporated under reduced pressure
  14. additionEthyl acetate was added
  15. customthe solid was precipitated
  16. filtrationfiltered
  17. customdried under vacuum

Sources & evidence

ORD record
ord-4f23b9f681db4e03aa7c2f395aef38d8
Source dataset
uspto-grants-2013_02
Patent number
US08377923B2

Reaction notes

Loading…