Hydrochloric Acid → 4-[(2-Hydroxyethyl)methylamino]-4-phenylcyclohexanone ethylene ketal hydrochloride

HRID 1462510Notes

Reaction equation

HRID 1462510 reaction equation
C(O[C:4]([CH2:6][N:7]([CH3:21])[C:8]1([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:13][CH2:12][C:11](=[O:14])[CH2:10][CH2:9]1)=[O:5])C.[H-].[Al+3].[Li+].[H-].[H-].[H-].[OH-].[Na+].[ClH:30].[CH2:31]([O:33]CC)[CH3:32]>O.O1CCCC1>[ClH:30].[CH2:32]1[O:14][C:11]2([CH2:10][CH2:9][C:8]([N:7]([CH2:6][CH2:4][OH:5])[CH3:21])([C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH2:13][CH2:12]2)[O:33][CH2:31]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 213909514-[[(Ethoxycarbonyl)methyl]methylamino]-4-phenylcyclohexanone2×

Product 1

HCID 867395454-[(2-Hydroxyethyl)methylamino]-4-phenylcyclohexanone ethylene ketal hydrochlorideYield 58%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution consisting of 4.52 gm. (0.0136 mole) of 4-[[(ethoxycarbonyl)methyl]methylamino]-4-phenylcyclohexanone, ethylene ketal, p-toluenesulfonate (prepared in Example 35, above), and 100 ml. tetrahydrofuran is added to a suspension of 0.52 gm. lithium aluminum hydride in 10 ml. tetrahydrofuran. This reaction is heated at the reaction mixture is heated at the reflux temperature for four (4) hours, after which heating it is allowed to cool and then chilled in an ice bath. To the chilled solution is added 0.52 ml. water followed by 0.52 ml. of 14% aqueous sodium hydroxide, and finally followed by another 1.56 ml. water. A gel forms and the gelatinous liquid is poured through a filter. The filtrate is collected and the liquids removed by evaporation under reduced pressure. The residue thus obtained is chromatographed on a 400 ml. column of silica gel and the chromatogram is developed by elution with a 3% solutin of methanol in methylene chloride which has been saturated with ammonia. The fractions containing the prospective product, as determined by thin layer chromatography, are combined and the solvents removed by evaporation under reduced pressure. The residue thus obtained is dissolved in diethyl ether and then hydrogen chloride saturated diethyl ether is added. A precipitate forms which is collected on a filter and recrystallized from a mixture of methylene chloride and ethyl acetate. There is thus obtained 2.56 gm. (58% yield) of 4-[(2-hydroxyethyl)methylamino]-4-phenylcyclohexanone ethylene ketal hydrochloride having a melting range from 184° to 186° C. A second crop of crystals obtained by removing some of the solvent mixture from the mother liquors by evaporation under reduced pressure weighs 0.56 gm. and has a melting range from 176° to 182° C.

Workup

  1. temperatureThis reaction is heated at the reaction mixture
  2. temperatureafter which heating it
  3. temperatureto cool
  4. temperaturechilled in an ice bath
  5. additionTo the chilled solution is added 0.52 ml
  6. additionA gel forms and the gelatinous liquid is poured through a filter
  7. customThe filtrate is collected
  8. customthe liquids removed by evaporation under reduced pressure
  9. customThe residue thus obtained
  10. customis chromatographed on a 400 ml
  11. washcolumn of silica gel and the chromatogram is developed by elution with a 3% solutin of methanol in methylene chloride which
  12. additionThe fractions containing the prospective product
  13. customthe solvents removed by evaporation under reduced pressure
  14. customThe residue thus obtained
  15. customA precipitate forms which is collected on
  16. filtrationa filter
  17. customrecrystallized from a mixture of methylene chloride and ethyl acetate

Sources & evidence

ORD record
ord-1728516981b24422873c9a9e03321717
Source dataset
uspto-grants-1984_07
Patent number
US04460604

Reaction notes

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