Water → HCID 13769240, compound

HRID 2232540Notes

Reaction equation

HRID 2232540 reaction equation
[C:1]([O:9]CC)(=[O:8])[CH2:2][C:3](OCC)=O.[H-].[Na+].BrC[C:16]1[N:17]=[C:18]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:19]2[C:24]([CH:25]=1)=[CH:23][CH:22]=[CH:21][CH:20]=2.O>O1CCCC1>[C:26]1([C:18]2[C:19]3[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH:25]=[C:16]([CH2:3][CH2:2][C:1]([OH:9])=[O:8])[N:17]=2)[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1

Participants

6

Reactant 4

HCID 962WaterHCID 7761Diethyl MalonateHCID 24758Sodium hydrideHCID 12424753HCID 12424753, compound

Product 1

HCID 13769240HCID 13769240, compoundYield 37.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of diethyl malonate (17.9 g) in anhydrous tetrahydrofuran (100 cc) is added dropwise under nitrogen to sodium hydride (3.36 g, 80% strength in oil) and anhydrous tetrahydrofuran (80 cc). After 1 hour's stirring, a solution of 3-bromomethyl-1-phenylisoquinoline (8.3 g) in tetrahydrofuran (100 cc) is added dropwise, and the mixture is left with stirring at room temperature (approximately 20° C.) for 1 hour. Water (200 cc) is added and the aqueous phase extracted with ethyl acetate (3×200 cc). The organic phase is dried over magnesium sulphate, filtered and evaporated to dryness under reduced pressure. The residue is chromatographed on silica gel with a cyclohexane/ethyl acetate (4:1 by volume) mixture as eluant. An oil (9.6 g) is recovered, taken up in concentrated hydrochloric acid (95 cc) and brought to boiling for 20 hours. After the mixture is cooled, water (200 cc) is added, the aqueous phase is washed with ethyl acetate (2×50 cc), potassium hydroxide solution is added until the pH is 5 and the mixture is extracted with chloroform (3×50 cc). The organic phase is dried over magnesium sulphate and evaporated to dryness under reduced pressure. 1-Phenyl-3-isoquinolinepropanoic acid (2.9 g), m.p. 146° C., is obtained.

Workup

  1. waitthe mixture is left
  2. stirringwith stirring at room temperature (approximately 20° C.) for 1 hour
  3. extractionthe aqueous phase extracted with ethyl acetate (3×200 cc)
  4. dry with materialThe organic phase is dried over magnesium sulphate
  5. filtrationfiltered
  6. customevaporated to dryness under reduced pressure
  7. customThe residue is chromatographed on silica gel with a cyclohexane/ethyl acetate (4:1 by volume) mixture as eluant
  8. customAn oil (9.6 g) is recovered
  9. waitto boiling for 20 hours
  10. temperatureAfter the mixture is cooled
  11. additionwater (200 cc) is added
  12. washthe aqueous phase is washed with ethyl acetate (2×50 cc), potassium hydroxide solution
  13. additionis added until the pH is 5
  14. extractionthe mixture is extracted with chloroform (3×50 cc)
  15. dry with materialThe organic phase is dried over magnesium sulphate
  16. customevaporated to dryness under reduced pressure

Sources & evidence

ORD record
ord-03162d61525142faa3a22f457f60a0cd
Source dataset
uspto-grants-1988_11
Patent number
US04788204

Reaction notes

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