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

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Reaction Steps

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.

Provenance & Evidence