反应详情

A mixture of 4-(4-benzyloxy-phenyl)-cyclohexanone (8.2 g, 29 mmol), benzyloxyhydroxylamine hydrochloride (4.7 g, 29 mmol) and ethanol was heated for 2 h. at reflux. The solvent was removed and the residue was crystallized to give white crystals (10.2 g, 90%) of the benzyloxy-oxime of 4-(4-benzyloxy-phenyl)-cyclohexanone. The latter was refluxed for 4 days with LiAlH4 (4 g, 105 mmol) in THF (300 ml). After the addition of H2O (30 ml), NaOH 15% (30 ml) and H2O (30 ml), the solids were removed by filtration and the filtrate evaporated. The residue was partioned between H2O and methylene chloride and the organic layer was dried and evaporated. The residue was purified by chromatography (SiO2, CH2Cl2—MeOH—aq.NH3 140:10:1) to give a mixture of cis and trans 4-(4-benzyloxy-phenyl)-cyclohexyl-amine (3.8 g) which was not separated at this stage. A portion of this mixture (1 g, 3.5 mmol) together with 2-phenoxyethyl bromide (0.78 g, 3.55 mmol), K2CO3 (1 g) and 2-butanone (20 ml) was refluxed for 3 days. The mixture was evaporated and H2O was added. Extraction with CH2Cl2 gave after drying and evaporation of the solvent a residue which was purified by chromatography (SiO2, CH2Cl2—MeOH 98:2) to give cis-[4-(4-benzyloxy-phenyl)-cyclohexyl]-(2-phenoxy-ethyl)-amine (140 mg, colorless oil, MS: m/e=402.5 (M+H+)) and trans-[4-(4-benzyloxy-phenyl)-cyclohexyl]-(2-phenoxy-ethyl)-amine (200 mg, white solid, Mp. 95-98°, MS: m/e=402.5 (M+H+)).

1. customthe solids were removed by filtration
2. customthe filtrate evaporated
3. customthe organic layer was dried
4. customevaporated
5. customThe residue was purified by chromatography (SiO2, CH2Cl2—MeOH—aq.NH3 140:10:1)
6. customto give
7. customwas not separated at this stage
8. customThe mixture was evaporated
9. additionH2O was added
10. extractionExtraction with CH2Cl2
11. customgave
12. customafter drying
13. customevaporation of the solvent a residue which
14. customwas purified by chromatography (SiO2, CH2Cl2—MeOH 98:2)