Sodium hydride → 3-(2-Hydroxy-3-(isopropylamino)propoxy)-2-phenylphthalimidine

HRID 1288247Notes

Reaction equation

HRID 1288247 reaction equation
[OH:1][CH:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[H-].[Na+].[O:20]1[CH2:27][CH:21]1[CH2:22][NH:23][CH:24]([CH3:26])[CH3:25]>CN(C)C=O.C(OCC)C.C(OC(C)C)(C)C>[OH:20][CH:21]([CH2:22][NH:23][CH:24]([CH3:26])[CH3:25])[CH2:27][O:11][CH:4]1[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[C:2](=[O:1])[N:3]1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 866702,3-Dihydro-3-hydroxy-2-phenyl-1H-isoindol-1-oneHCID 13462320N-(oxiran-2-ylmethyl)propan-2-amine

Product 1

HCID 509723-(2-Hydroxy-3-(isopropylamino)propoxy)-2-phenylphthalimidineYield 13.2%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent2×HCID 7914Diisopropyl EtherSolvent

Procedure

A solution of 3-hydroxy-2-phenyl-isoindolin-1-one (6.75 g.) in anhydrous dimethylformamide (20 cc.) is added to a suspension of sodium hydride (50% dispersion in mineral oil) (1.48 g.) in anhydrous dimethylformamide (20 cc.). When the evolution of gas has ceased, 2,3-epoxy-1-isopropylamino-propane (3.8 g.) is added whilst keeping the temperature at about 5° C. After the end of the addition, stirring is continued for a further 24 hours at a temperature of about 20° C. and then the reaction mixture is poured into ice-water (250 cc.). The insoluble oily product is extracted with methylene chloride (3 × 100 cc.). The solution obtained is dried over sodium sulphate and then concentrated to dryness under reduced pressure. The oily residue is taken up in diethyl ether (50 cc.) and the insoluble product is filtered off and then washed with diethyl ether (30 cc.). The filtrate is then extracted with 0.5N hydrochloric acid (60 cc.). The acid solution obtained is washed with diethyl ether (20 cc.) and then rendered alkaline by the addition of 1N sodium hydroxide solution (30 cc.). The insoluble oily product is extracted with diethyl ether (2 × 50 cc.) and the solution obtained is dried over sodium sulphate and then concentrated to dryness under reduced pressure. The oily product obtained is dissolved in a mixture of diethyl ether and di-isopropyl ether (1/1 by volume; 20 cc.), and the product which crystallises is filtered off and then washed with a mixture of diethyl ether and di-isopropyl ether (1/1 by volume; 5 cc.). After drying, 3-(2-hydroxy-3-isopropylamino-propoxy)-2-phenyl-isoindolin-1-one (1.35 g.), melting at 92° C., is obtained.

Workup

  1. customat about 5° C
  2. additionAfter the end of the addition
  3. extractionThe insoluble oily product is extracted with methylene chloride (3 × 100 cc.)
  4. customThe solution obtained
  5. dry with materialis dried over sodium sulphate
  6. concentrationconcentrated to dryness under reduced pressure
  7. filtrationthe insoluble product is filtered off
  8. washwashed with diethyl ether (30 cc.)
  9. extractionThe filtrate is then extracted with 0.5N hydrochloric acid (60 cc.)
  10. customThe acid solution obtained
  11. washis washed with diethyl ether (20 cc.)
  12. additionby the addition of 1N sodium hydroxide solution (30 cc.)
  13. extractionThe insoluble oily product is extracted with diethyl ether (2 × 50 cc.)
  14. customthe solution obtained
  15. dry with materialis dried over sodium sulphate
  16. concentrationconcentrated to dryness under reduced pressure
  17. customThe oily product obtained
  18. customthe product which crystallises
  19. filtrationis filtered off
  20. washwashed with a mixture of diethyl ether and di-isopropyl ether (1/1 by volume; 5 cc.)
  21. customAfter drying

Sources & evidence

ORD record
ord-d5d86400f28f4d319cbc7a2e6b7b03bf
Source dataset
uspto-grants-1976_10
Patent number
US03987174

Reaction notes

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