1-Methylpiperazine → HCID 86734087, compound

HRID 1288250Notes

Reaction equation

HRID 1288250 reaction equation
[O:1]1[CH2:21][CH:2]1[CH2:3][O:4][CH:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7](=[O:14])[N:6]1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[CH3:22][N:23]1[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1>C1(C)C=CC=CC=1>[OH:1][CH:2]([CH2:21][N:26]1[CH2:27][CH2:28][N:23]([CH3:22])[CH2:24][CH2:25]1)[CH2:3][O:4][CH:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7](=[O:14])[N:6]1[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

Participants

4

Reactant 2

HCID 531671-MethylpiperazineHCID 64522163-[(Oxiran-2-yl)methoxy]-2-phenyl-2,3-dihydro-1H-isoindol-1-one

Product 1

HCID 86734087HCID 86734087, compoundYield 127.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of 3-(2,3-epoxypropoxy)-2-phenyl-isoindolin-1-one (8.4 g.) and 1-methylpiperazine (3.6 g.) in anhydrous toluene (84 cc.) is heated under reflux for 3 days. After cooling, the reaction mixture is washed with water (2 × 50 cc.) and then the organic solution is extracted with 1N hydrochloric acid (55 cc.) and water (3 × 20 cc.). The aqueous and acid solutions are combined and are rendered alkaline by addition of 1N sodium hydroxide solution (55 cc.). The oil which separates out is extracted with methylene chloride (150 cc.) and then the organic solution obtained is dried over sodium sulphate and concentrated to dryness under reduced pressure. The residual oil is dissolved in ethanol (20 cc.) and the resulting solution is added to a hot solution of fumaric acid (5.85 g.) in ethanol (80 cc.). The product which crystallises on cooling is filtered off and then washed with ethanol (30 cc.) and di-isopropyl ether (40 cc.). After drying, 3-[2-hydroxy-3-(4-methylpiperazin-1-yl)-propoxy]-2-phenyl-isoindolin-1-one acid difumarate (14.5 g.), melting at 194° C., is obtained.

Workup

  1. temperatureunder reflux for 3 days
  2. temperatureAfter cooling
  3. washthe reaction mixture is washed with water (2 × 50 cc.)
  4. extractionthe organic solution is extracted with 1N hydrochloric acid (55 cc.) and water (3 × 20 cc.)
  5. additionby addition of 1N sodium hydroxide solution (55 cc.)
  6. extractionThe oil which separates out is extracted with methylene chloride (150 cc.)
  7. customthe organic solution obtained
  8. dry with materialis dried over sodium sulphate
  9. concentrationconcentrated to dryness under reduced pressure
  10. dissolutionThe residual oil is dissolved in ethanol (20 cc.)
  11. additionthe resulting solution is added to a hot solution of fumaric acid (5.85 g.) in ethanol (80 cc.)
  12. customThe product which crystallises
  13. temperatureon cooling
  14. filtrationis filtered off
  15. washwashed with ethanol (30 cc.) and di-isopropyl ether (40 cc.)
  16. customAfter drying

Sources & evidence

ORD record
ord-c4932d8948834bf981e16c05066ec9b4
Source dataset
uspto-grants-1976_10
Patent number
US03987174

Reaction notes

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