Water → HCID 13769244, compound

HRID 2232516Notes

Reaction equation

HRID 2232516 reaction equation
[H-].[Na+].[CH3:3][CH:4]([C:10](OCC)=O)[C:5]([O:7]CC)=[O:6].BrC[C:17]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:20]=[C:19]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[N:18]=1.O>O1CCCC1>[CH3:3][CH:4]([CH2:10][C:17]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:20]=[C:19]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[N:18]=1)[C:5]([OH:7])=[O:6]

Participants

6

Reactant 4

HCID 962WaterHCID 11857Diethyl methylmalonateHCID 24758Sodium hydrideHCID 13769241HCID 13769241, compound

Product 1

HCID 13769244HCID 13769244, compoundYield 72.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

Sodium hydride (2.1 g, 60% strength in oil) and anhydrous tetrahydrofuran (50 cc) are placed under nitrogen. A solution of diethyl methylmalonate (9.1 g) in anhydrous tetrahydrofuran (50 cc) is added dropwise. Stirring is continued for 1 hour at room temperature (approximately 20° C.) and a solution of 1-bromomethyl-3-phenylisoquinoline (10.4 g) in anhydrous tetrahydrofuran (100 cc) is added. After 20 hours of contact, water (200 cc) is added and the aqueous phase extracted with ethyl acetate (3×50 cc). After removal of the solvents under reduced pressure, the product (19 g) recovered is brought to boiling for 20 hours in concentrated hydrochloric acid (70 cc) and acetic acid (70 cc). After being cooled, the mixture is poured into water (1000 cc) and alkalinised to pH 10 with sodium hydroxide solution, and the aqueous phase is washed with ethyl acetate (100 cc) acidified with hydrochloric acid and extracted with chloroform (3×200 cc). The organic phase is dried over magnesium sulphate, filtered and evaporated to dryness under reduced pressure. α-Methyl-3-phenyl-1isoquinolinepropanoic acid (7.4 g), m.p. 184° C., is obtained.

Workup

  1. extractionthe aqueous phase extracted with ethyl acetate (3×50 cc)
  2. customAfter removal of the solvents under reduced pressure
  3. customthe product (19 g) recovered
  4. waitto boiling for 20 hours in concentrated hydrochloric acid (70 cc)
  5. temperatureAfter being cooled
  6. additionthe mixture is poured into water (1000 cc)
  7. washthe aqueous phase is washed with ethyl acetate (100 cc)
  8. extractionextracted with chloroform (3×200 cc)
  9. dry with materialThe organic phase is dried over magnesium sulphate
  10. filtrationfiltered
  11. customevaporated to dryness under reduced pressure

Sources & evidence

ORD record
ord-21bc9d0e936643388b82d6c06e881fe1
Source dataset
uspto-grants-1988_11
Patent number
US04788199

Reaction notes

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