Tetrahydrofuran → HCID 4247613, compound

HRID 1945240Notes

Reaction equation

HRID 1945240 reaction equation
[C:1]([CH2:3][N:4]1[CH2:8][CH2:7][N:6]([CH2:9][C:10]#[N:11])[CH:5]1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)#[N:2].[CH2:18]1[CH2:22]O[CH2:20][CH2:19]1>>[CH:20](=[N:11][CH2:10][CH2:9][N:6]1[CH2:7][CH2:8][N:4]([CH2:3][CH2:1][N:2]=[CH:22][C:18]2[CH:16]=[CH:15][CH:14]=[CH:20][CH:19]=2)[CH:5]1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:19]1[CH:13]=[CH:12][CH:5]=[CH:22][CH:18]=1

Participants

3

Reactant 2

HCID 8028TetrahydrofuranHCID 11514112HCID 11514112, compound

Product 1

HCID 4247613HCID 4247613, compoundYield 84.85%

Conditions

Temperature
40 °C

Procedure

1 equal mole of (3-cyanomethyl-2-phenyl-imidazolidin-1-yl)-acetonitrile and THF were mixed in a reactor and the reactor was purged with nitrogen gas. The reaction mixture was then transferred to a feeding vessel. The reactor was washed with THF and the solution was added into the mixture in the feeding vessel. 3 equal moles of LiAlH4 in THF solution was added to the reactor. 4 equal moles of methanol and THF were mixed in another feeding vessel, this mixture was added over the next 40 minutes at an internal temperature of 35 to 40° C. into the main reaction mixture. The solution was then heated to an internal temperature of 40° C. under constant stirring for one additional hour. The mixture of methanol and THF was slowly added to the mixture in the feeding vessel at an internal temperature of 39° C.-45° C. The mixture was stirred at an internal temperature of 40° C. for an additional 30 minutes. The mixture was then cooled to an internal temperature of 10° C. within 1 hour. Na2SO4 and NaOH were added to the reaction mixture. Saturated Na2CO3-solution was added at an internal temperature of 10-18° C. via a feeding vessel. The reaction mixture was stirred at an internal temperature of 10° C. overnight. Na2HPO4 was added to the mixture and the reaction suspension was filtered into the stirring vessel. The filter cake was washed with two volumes of THF. The suspension of Na2HPO4 and the filtrate was stirred for one hour in the stirring vessel and then filtered over a nutsch. The filter cake was washed with THF. Both filtrates (filtration and washing) were then transferred into the second reactor (via inline-filter). 2 equal moles of benzaldehyde was added to the filtrate at 20° C. (via inline filter). THF was distilled off at an internal temperature of 10-20° C. and at a pressure of 130-210 mbar, external temperature (ET)=50° C. Hexane was then added (ET=40° C.) to the mixture. Water was then distilled off at an internal temperature of 16-20° C., with a pressure of 170-190 mbar and a AT of 40-43° C. The hexane was further distilled off at an internal temperature of 16° C., at a pressure of 160-180 mbar and ET=44° C. Isopropanol was added to the reactor via a feeding vessel. Isopropanol was distilled off at IT=10-27° C., p=30-114 mbar and ET=50° C. The reaction mixture was stirred for an hour at an internal temperature of 35° C. The reaction mixture was then cooled to −5° C. and stirred overnight. The nutsch was again purged with nitrogen and the suspension was again filtered. The filter cake was washed with cold (6° C.) isopropanol. The product, benzylidene-(2-{3-[2-(benzylidene-amino)-ethyl]-2-phenyl-imidazolidin-1-yl}-ethyl)-amine, was allowed to dry in a PROVATECH dryer at a temperature of 30-40° C. at a pressure of less than or equal to 30 mbar. The reaction was carried out in five independent reaction vessels with the following results: Flask 1 gave benzylidene-(2-{3-[2-(benzylidene-amino)-ethyl]-2-phenyl-imidazolidin-1-yl}-ethyl)-amine as an off-white solid with a purity of 99.93% as measured by gas chromatography, which represented a total yield of 84.85%. Flask 2 gave benzylidene-(2-{3-[2-(benzylidene-amino)-ethyl]-2-phenyl-imidazolidin-1-yl}-ethyl)-amine as an off-white solid with a purity of 99.42% as measured by gas chromatography, which represented a total yield of 77.1%. Flask 3 gave benzylidene-(2-{3-[2-(benzylidene-amino)-ethyl]-2-phenyl-imidazolidin-1-yl}-ethyl)-amine as an off-white solid with a purity of 99.89% as measured by gas chromatography, which represented a total yield of 78.3%. Flask 4 gave benzylidene-(2-{3-[2-(benzylidene-amino)-ethyl]-2-phenyl-imidazolidin-1-yl}-ethyl)-amine as an off-white solid with a purity of 99.87% as measured by gas chromatography, which represented a total yield of 82.7%.

Workup

  1. customthe reactor was purged with nitrogen gas
  2. customThe reaction mixture was then transferred to a feeding vessel
  3. washThe reactor was washed with THF
  4. additionthe solution was added into the mixture in the feeding vessel
  5. addition3 equal moles of LiAlH4 in THF solution was added to the reactor
  6. addition4 equal moles of methanol and THF were mixed in another feeding vessel
  7. additionthis mixture was added over the next 40 minutes at an internal temperature of 35 to 40° C. into the main reaction mixture
  8. additionThe mixture of methanol and THF
  9. additionwas slowly added to the mixture in the feeding vessel at an internal temperature of 39° C.-45° C
  10. stirringThe mixture was stirred at an internal temperature of 40° C. for an additional 30 minutes
  11. temperatureThe mixture was then cooled to an internal temperature of 10° C. within 1 hour
  12. additionNa2SO4 and NaOH were added to the reaction mixture
  13. additionSaturated Na2CO3-solution was added at an internal temperature of 10-18° C. via a feeding vessel
  14. stirringThe reaction mixture was stirred at an internal temperature of 10° C. overnight
  15. additionNa2HPO4 was added to the mixture
  16. filtrationthe reaction suspension was filtered into the stirring vessel
  17. washThe filter cake was washed with two volumes of THF
  18. additionThe suspension of Na2HPO4
  19. stirringthe filtrate was stirred for one hour in the stirring vessel
  20. filtrationfiltered over a nutsch
  21. washThe filter cake was washed with THF
  22. filtrationBoth filtrates (filtration and washing)
  23. filtrationwere then transferred into the second reactor (via inline-filter)
  24. addition2 equal moles of benzaldehyde was added to the filtrate at 20° C.
  25. filtration(via inline filter)
  26. distillationTHF was distilled off at an internal temperature of 10-20° C. and at a pressure of 130-210 mbar, external temperature (ET)=50° C
  27. additionHexane was then added (ET=40° C.) to the mixture
  28. distillationWater was then distilled off at an internal temperature of 16-20° C., with a pressure of 170-190 mbar
  29. customa AT of 40-43° C
  30. distillationThe hexane was further distilled off at an internal temperature of 16° C., at a pressure of 160-180 mbar and ET=44° C
  31. additionIsopropanol was added to the reactor via a feeding vessel
  32. distillationIsopropanol was distilled off at IT=10-27° C., p=30-114 mbar and ET=50° C
  33. stirringThe reaction mixture was stirred for an hour at an internal temperature of 35° C
  34. temperatureThe reaction mixture was then cooled to −5° C.
  35. stirringstirred overnight
  36. customThe nutsch was again purged with nitrogen
  37. filtrationthe suspension was again filtered
  38. washThe filter cake was washed with cold (6° C.) isopropanol
  39. customto dry in a PROVATECH dryer at a temperature of 30-40° C. at a pressure of less than or equal to 30 mbar
  40. customThe reaction was carried out in five independent reaction vessels with the
  41. customfollowing results

Sources & evidence

ORD record
ord-efd027927ea741379a13f966964a8461
Source dataset
uspto-grants-2013_03
Patent number
US08394992B2

Reaction notes

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