Reaction #1178405

Reaction equation

(Z)-4-oxo-5-azaundec-2-enedioic acid

acetic anhydride

phenothiazine

HCl

water

→

desired product

N-Succinimidyl 6-Maleimidohexanoate

Solvents

THF

Triethylamine

Conditions

Workup

1. 1
   Otherequipped with an overhead stirrer
2. 2
   Temperaturethe mixture was heated
3. 3
   Temperatureto reflux
4. 4
   TemperatureAfter a total of 4 hours of reflux
5. 5
   workup.STIRRINGThe mixture was stirred 3 hours at room temperature
6. 6
   Filtrationwas filtered through a filtration pad (Celite 545, J. T. Baker, Jackson, Tenn.)
7. 7
   Otherto remove solids
8. 8
   ExtractionThe filtrate was extracted with 4×500 ml of chloroform
9. 9
   Dryingthe combined extracts were dried over sodium sulfate
10. 10
    workup.ADDITIONAfter adding 15 mg of phenothiazine
11. 11
    Otherpolymerization
12. 12
    Otherthe solvent was removed under reduced pressure
13. 13
    OtherThe 6-maleimidohexanoic acid was recrystallized from 2:1 hexane
14. 14
    Otherchloroform to give typical
15. 15
    Otheryields of 76-83 g (55-60%) with a melting point of 81-85° C

Procedure

(Z)-4-oxo-5-azaundec-2-enedioic acid, 150.0 g (0.654 moles), acetic anhydride, 68 ml (73.5 g, 0.721 moles), and phenothiazine, 500 mg, were added to a 2 liter three-neck round bottom flask equipped with an overhead stirrer. Triethylamine, 91 ml (0.653 moles), and 600 ml of THF were added and the mixture was heated to reflux while stirring. After a total of 4 hours of reflux, the dark mixture was cooled to about 60° C. and poured into a solution of 250 ml of 12 N HCl in 3 liters of water. The mixture was stirred 3 hours at room temperature and then was filtered through a filtration pad (Celite 545, J. T. Baker, Jackson, Tenn.) to remove solids. The filtrate was extracted with 4×500 ml of chloroform and the combined extracts were dried over sodium sulfate. After adding 15 mg of phenothiazine to prevent polymerization, the solvent was removed under reduced pressure. The 6-maleimidohexanoic acid was recrystallized from 2:1 hexane:chloroform to give typical yields of 76-83 g (55-60%) with a melting point of 81-85° C. Analysis on a NMR spectrometer was consistent with the desired product: 1H NMR (CDCl3) maleimide protons 6.55 (s, 2H), methylene adjacent to nitrogen 3.40 (t, 2H), methylene adjacent to carbonyl 2.30 (t, 2H), and remaining methylenes 1.05-1.85 (m, 6H).

Source