N-Hydroxyphthalimide → N-[3-(4-Methyl-1-piperazinyl)propoxy]phthalimide

HRID 1533870Notes

Reaction equation

HRID 1533870 reaction equation
[OH:1][CH2:2][CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][N:8]([CH3:11])[CH2:7][CH2:6]1.O[N:13]1[C:17](=[O:18])[C:16]2=[CH:19][CH:20]=[CH:21][CH:22]=[C:15]2[C:14]1=[O:23].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC([O-])=O>O1CCCC1>[CH3:11][N:8]1[CH2:7][CH2:6][N:5]([CH2:4][CH2:3][CH2:2][O:1][N:13]2[C:14](=[O:23])[C:15]3=[CH:22][CH:21]=[CH:20][CH:19]=[C:16]3[C:17]2=[O:18])[CH2:10][CH2:9]1

Participants

6

Reactant 4

HCID 10665N-HydroxyphthalimideHCID 11776TriphenylphosphineHCID 792083-(4-Methyl-1-piperazine)propan-1-olHCID 86599450N-ethoxycarbonyliminocarbamate

Product 1

HCID 19911312N-[3-(4-Methyl-1-piperazinyl)propoxy]phthalimideYield 74.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
20 °C

Procedure

N-[3-(4-Methyl-1-piperazinyl)propoxy]phthalimide may be obtained in the following manner: a solution of 1-(3-hydroxypropyl)-4-methylpiperazine (8.4 g), N-hydroxyphthalimide (8.2 g) and triphenylphosphine (13.1 g) in tetrahydrofuran (120 cc) is cooled to a temperature in the region of 0° C. and ethyl azodicarboxylate (10.1 g) is added in the course of 30 minutes. The solution obtained is stirred at a temperature in the region of 20° C. for 18 hours and is then concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature in the region of 60° C. The crude oil obtained is chromatographed on a column 5 cm in diameter containing silica (0.063-0.2 mm) (400 g). The column is eluted with mixtures of ethyl acetate and methanol, collecting 500-cc fractions. The first 5 fractions originating from elution with pure ethyl acetate and the next 5 fractions originating from elution with a mixture of ethyl acetate and methanol (70:30 by volume) are discarded. The next fraction originating from elution with a mixture of ethyl acetate and methanol (70:30 by volume), the next 5 fractions originating from elution with a mixture of ethyl acetate and methanol (50:50 by volume) and the next 2 fractions originating from elution with pure methanol are combined and concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature in the region of 60° C. N-[3-(4-Methyl-1-piperazinyl)propoxy]phthalimide (11.4 g) is thereby obtained in the form of a red oil (Rf=0.2; thin-layer chromatography on silica, eluent: ethyl acetate/methanol, 50:50 by volume).

Workup

  1. additionis added in the course of 30 minutes
  2. customThe solution obtained
  3. concentrationis then concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature in the region of 60° C
  4. customThe crude oil obtained
  5. customis chromatographed on a column 5 cm in diameter
  6. additioncontaining silica (0.063-0.2 mm) (400 g)
  7. washThe column is eluted with mixtures of ethyl acetate and methanol
  8. customcollecting 500-cc fractions
  9. washThe first 5 fractions originating from elution with pure ethyl acetate
  10. washthe next 5 fractions originating from elution with a mixture of ethyl acetate and methanol (70:30 by volume)
  11. washThe next fraction originating from elution
  12. additionwith a mixture of ethyl acetate and methanol (70:30 by volume)
  13. washthe next 5 fractions originating from elution with a mixture of ethyl acetate and methanol (50:50 by volume)
  14. washthe next 2 fractions originating from elution with pure methanol
  15. concentrationconcentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature in the region of 60° C

Sources & evidence

ORD record
ord-098dc36dd5274d67921c6bb8b47433dd
Source dataset
uspto-grants-1992_02
Patent number
US05086051

Reaction notes

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