Benzyl chloroformate → 2,3(1H)-Isoquinolinedicarboxylic acid, 3,4-dihydro-, 2-(phenylMethyl) ester

HRID 1609614Notes

Reaction equation

HRID 1609614 reaction equation
[C:1]([CH:4]1[CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH2:6][NH:5]1)([OH:3])=[O:2].[C:14](Cl)(=[O:23])[O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>[OH-].[Na+]>[C:14]([N:5]1[CH:4]([C:1]([OH:3])=[O:2])[CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH2:6]1)([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:23]

Participants

4

Reactant 2

HCID 10387Benzyl chloroformateHCID 954891,2,3,4-Tetrahydroisoquinoline-3-carboxylic acid

Product 1

HCID 42347112,3(1H)-Isoquinolinedicarboxylic acid, 3,4-dihydro-, 2-(phenylMethyl) ester

Reagents, catalysts & solvents 1

HCID 14798Sodium HydroxideSolvent2×

Procedure

188 g (1.05 moles) of 3-carboxy-1,2,3,4-tetrahydroisoquinoline are added to 1,050 ml of 1N NaOH at 0°, and 160 ml of benzyl chlorocarbonate and a further 1,050 ml of 1N NaOH are then simultaneously added dropwise at this temperature, whilst stirring. The mixture is then stirred for 2 hours at room temperature and extracted three times with ether, and the alkaline/aqueous phase is acidified to pH 1 with concentrated HCl. The oil which separates out is extracted with ethyl acetate. The ethyl acetate solution is washed with water until the water phase has a pH of 3.0. After the ethyl acetate solution has been dried over sodium sulfate, the product crystallizes from this solution after concentration and trituration. 1.5 liters of diisopropyl ether are added to the suspension of crystals, and the latter is stirred for one hour at room temperature, and filtered under suction. The product is dried over phosphorus pentoxide in a high vacuum. Yield: 256.7 g Melting point 138°-39° C.

Workup

  1. stirringThe mixture is then stirred for 2 hours at room temperature
  2. extractionextracted three times with ether
  3. extractionThe oil which separates out is extracted with ethyl acetate
  4. washThe ethyl acetate solution is washed with water until the water phase
  5. dry with materialAfter the ethyl acetate solution has been dried over sodium sulfate
  6. customthe product crystallizes from this solution
  7. concentrationafter concentration and trituration
  8. addition1.5 liters of diisopropyl ether are added to the suspension of crystals
  9. stirringthe latter is stirred for one hour at room temperature
  10. filtrationfiltered under suction
  11. dry with materialThe product is dried over phosphorus pentoxide in a high vacuum

Sources & evidence

ORD record
ord-214b1ca5022f4900b904a91c62c87b78
Source dataset
uspto-grants-1995_03
Patent number
US05401766

Reaction notes

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