Hydrochloric Acid → HCID 178464517, compound

HRID 1657570Notes

Reaction equation

HRID 1657570 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[CH2:13][CH2:12][C@H:11]([NH:14][C:15](=O)[CH3:16])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].[OH-].[Na+].[ClH:26]>CCOCC.CO.O.O1CCCC1>[ClH:26].[ClH:26].[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([C@H:8]2[CH2:13][CH2:12][C@H:11]([NH:14][CH2:15][CH3:16])[CH2:10][CH2:9]2)=[CH:6][CH:7]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 178474953HCID 178474953, compound

Product 1

HCID 178464517HCID 178464517, compoundYield 80%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 4 g. of trans N-[4-(p-aminophenyl)cyclohexyl]acetamide (prepared as in Example 83) in 150 ml. of tetrahydrofuran is added to 1.4 g. of lithium aluminum hydride in 10 ml. of tetrahydrofuran. The mixture is heated at reflux for about 3 hours and allowed to stand for about 16 hours. The cooled mixture is then heated with 1.4 ml. of water and 1.4 ml. of 15% aqueous sodium hydroxide solution and an additional 1.4 ml. of water. The solid is removed on a filter and the filtrate evaporated to dryness. The residual oily solid is suspended in ether. This mixture is filtered to give 0.63 g. of starting material melting at 190° to 194° C. The filtrate is evaporated to dryness and the residue dissolved in 75 ml. of tetrahydrofuran and added to 2 g. of lithium aluminum hydride in 200 ml. of tetrahydrofuran. After about 17 hours of heating at reflux temperature and about 17 hours at room temperature, the cooled mixture is heated with 2 ml. of water and 2 ml. of 15% aqueous sodium hydroxide solution and an additional 2 ml. of water. The solid is removed on a filter and the filtrate evaporated to dryness to give the crude product, which is dissolved in 50 ml. of methanol and then treated with 6.5 ml. of 4.7N hydrochloric acid in ether. The solution is evaporated to dryness and the residue recrystallized from methanol:ethyl acetate to give 3.55 g. (80% yield) of trans 4-(p-aminophenyl)-N-ethylcyclohexylamine dihydrochloride melting at 291° to 295° C.

Workup

  1. temperatureThe mixture is heated
  2. temperatureat reflux for about 3 hours
  3. temperatureThe cooled mixture is then heated with 1.4 ml
  4. customThe solid is removed on
  5. filtrationa filter
  6. customthe filtrate evaporated to dryness
  7. filtrationThis mixture is filtered
  8. customto give 0.63 g
  9. customThe filtrate is evaporated to dryness
  10. dissolutionthe residue dissolved in 75 ml
  11. additionof tetrahydrofuran and added to 2 g
  12. temperatureAfter about 17 hours of heating
  13. temperaturethe cooled mixture is heated with 2 ml
  14. customThe solid is removed on
  15. filtrationa filter
  16. customthe filtrate evaporated to dryness
  17. customto give the crude product, which
  18. dissolutionis dissolved in 50 ml
  19. customThe solution is evaporated to dryness
  20. customthe residue recrystallized from methanol
  21. customethyl acetate to give 3.55 g

Sources & evidence

ORD record
ord-db0d5afaa12644f584f3f5af96a71a70
Source dataset
uspto-grants-1976_06
Patent number
US03960961

Reaction notes

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