Pyrrolidine → HCID 70490736, compound

HRID 485827Notes

Reaction equation

HRID 485827 reaction equation
Cl.[C:2]1([CH:8]2[C:17]3[C:12](=[C:13](Cl)[CH:14]=[CH:15][CH:16]=3)[CH:11]([NH:19][C:20](=[O:22])[CH3:21])[N:10]([CH3:23])[CH2:9]2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH:24]1[CH2:28][CH2:27][CH2:26][CH2:25]1.C(O)(=O)/C=C\C(O)=O>C(O)C>[C:2]1([CH:8]2[C:17]3[C:12](=[C:13]([N:24]4[CH2:28][CH2:27][CH2:26][CH2:25]4)[CH:14]=[CH:15][CH:16]=3)[CH:11]([NH:19][C:20](=[O:22])[CH3:21])[N:10]([CH3:23])[CH2:9]2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 31268PyrrolidineHCID 444266Maleic AcidHCID 70490882HCID 70490882, compound

Product 1

HCID 70490736HCID 70490736, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

A mixture of 7.0 g (0.02 mole) of 4-phenyl-8-chloro-acetylamino-2-methyl-1,2,3,4-tetrahydro-isoquinoline-hydrochloride, 70 ml of ethanol and 20 ml (17.0 g, 0.24 mole) of pyrrolidine is refluxed for 5 hours. The reaction mixture is evaporated in vacuo, the residue is dissolved in a mixture of 100 ml of water and 100 ml of ether and the mixture is made alkaline by adding 30 ml of a 30% aqueous sodium hydroxide solution under cooling and stirring. The layers are separated, the aqueous phase is extracted five times with 100 ml of ether each, the organic phase is dried over anhydrous sodium sulfate, clarified with activated charcoal and evaporated. The residue is dissolved in 100 ml of warm ethanol and a solution of 6.6 g (0.057 mole) of maleic acid and 40 ml of ethanol is added. The product is precipitated by adding 1000 ml of ether. The sticky solid dimaleate salt is dissolved in 100 ml of water and the solution is made alkaline by adding 60 ml of a 30% aqueous sodium hydroxide solution under cooling and stirring. The aqueous layer is extracted once with 200 ml and four times with 100 ml of ether each. The ether phases are united, dried over anhydrous sodium sulfate and clarified with activated charcoal. The ether is evaporated and the residue is washed with a mixture of ether and petrolether. Thus 5.4 g of 4-phenyl-2-methyl-8-pyrrolidino-acetylamino-1,2,3,4-tetrahydro-isoquinoline are obtained in the form of white crystals (0.0154 mole). Mp.: 130° C.

Workup

  1. temperatureis refluxed for 5 hours
  2. customThe reaction mixture is evaporated in vacuo
  3. dissolutionthe residue is dissolved in a mixture of 100 ml of water and 100 ml of ether
  4. additionby adding 30 ml of a 30% aqueous sodium hydroxide solution
  5. temperatureunder cooling
  6. customThe layers are separated
  7. extractionthe aqueous phase is extracted five times with 100 ml of ether each, the organic phase
  8. dry with materialis dried over anhydrous sodium sulfate
  9. customevaporated
  10. dissolutionThe residue is dissolved in 100 ml of warm ethanol
  11. customThe product is precipitated
  12. additionby adding 1000 ml of ether
  13. dissolutionThe sticky solid dimaleate salt is dissolved in 100 ml of water
  14. additionby adding 60 ml of a 30% aqueous sodium hydroxide solution
  15. temperatureunder cooling
  16. stirringstirring
  17. extractionThe aqueous layer is extracted once with 200 ml and four times with 100 ml of ether each
  18. dry with materialdried over anhydrous sodium sulfate
  19. customThe ether is evaporated
  20. washthe residue is washed with a mixture of ether and petrolether

Sources & evidence

ORD record
ord-f10bff0652ae40c396415e35b7aec180
Source dataset
uspto-grants-1985_08
Patent number
US04537895

Reaction notes

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