Water → HCID 13769242, compound

HRID 2232509Notes

Reaction equation

HRID 2232509 reaction equation
[H-].[Na+].[C:3]([O:11]CC)(=[O:10])[CH2:4][C:5](OCC)=O.BrC[C:16]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:19]=[C:18]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[N:17]=1.O>O1CCCC1>[C:26]1([C:18]2[N:17]=[C:16]([CH2:5][CH2:4][C:3]([OH:11])=[O:10])[C:25]3[C:20]([CH:19]=2)=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

6

Reactant 4

HCID 962WaterHCID 7761Diethyl MalonateHCID 24758Sodium hydrideHCID 13769241HCID 13769241, compound

Product 1

HCID 13769242HCID 13769242, compoundYield 44.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
20 °C

Procedure

Sodium hydride (6.5 g, 80% strength in oil) is placed with tetrahydrofuran (160 cc) under nitrogen, and a solution of diethyl malonate (34.9 g) in anhydrous tetrahydrofuran (200 cc) is added dropwise. After 1 hour's stirring at room temperature (approximately 20° C.), a solution of 1-bromomethyl-3-phenylisoquinoline (16.2 g) in anhydrous tetrahydrofuran (200 cc) is added. After 20 hours' stirring at 20° C., water (200 cc) is added and the aqueous phase extracted with ethyl acetate. The organic phase is dried and evaporated to dryness under reduced pressure. The residual product is chromatographed on silica gel with a cyclohexane/ethyl acetate (8:2 by volume) mixture as eluant. The product (11.5 g) is recovered, taken up in concentrated hydrochloric acid (115 cc) and brought to boiling for 20 hours. Water (200 cc) is added, and the precipitate is filtered off and washed with water and acetone. 3-Phenyl-1-isoquinolinepropanoic acid (6.7 g) m.p. 160° C., is obtained.

Workup

  1. stirringAfter 20 hours' stirring at 20° C.
  2. extractionthe aqueous phase extracted with ethyl acetate
  3. customThe organic phase is dried
  4. customevaporated to dryness under reduced pressure
  5. customThe residual product is chromatographed on silica gel with a cyclohexane/ethyl acetate (8:2 by volume) mixture as eluant
  6. customThe product (11.5 g) is recovered
  7. waitto boiling for 20 hours
  8. additionWater (200 cc) is added
  9. filtrationthe precipitate is filtered off
  10. washwashed with water and acetone

Sources & evidence

ORD record
ord-e0c25185bbc54c7c99558c61068981df
Source dataset
uspto-grants-1988_11
Patent number
US04788199

Reaction notes

Loading…