Potassium Carbonate → HCID 178420396, compound

HRID 634770Notes

Reaction equation

HRID 634770 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].[OH-].[Na+].[CH2:9]([O:16][C:17]1[CH:22]=[CH:21][C:20]([C@H:23]2[CH2:28][CH2:27][C@H:26]([NH2:29])[CH2:25][CH2:24]2)=[CH:19][CH:18]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[O:30]([CH2:37][CH2:38]Br)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.C([O-])([O-])=O.[K+].[K+]>C1COCC1.CC(=O)CC.O>[CH2:9]([O:16][C:17]1[CH:18]=[CH:19][C:20]([C@@H:23]2[CH2:28][CH2:27][C@H:26]([NH:29][CH2:38][CH2:37][O:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[CH2:25][CH2:24]2)=[CH:21][CH:22]=1)[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1.[CH2:9]([O:16][C:17]1[CH:18]=[CH:19][C:20]([C@H:23]2[CH2:28][CH2:27][C@H:26]([NH:29][CH2:38][CH2:37][O:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[CH2:25][CH2:24]2)=[CH:21][CH:22]=1)[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1

Participants

10

Reactant 5

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 68526Benzene, (2-bromoethoxy)-HCID 21226445Aluminium lithium hydrideHCID 178511501HCID 178511501, compound

Product 2

HCID 178420396HCID 178420396, compoundHCID 178420397HCID 178420397, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6569Methyl Ethyl KetoneSolventHCID 8028TetrahydrofuranSolvent

Procedure

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+)).

Workup

  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)

Sources & evidence

ORD record
ord-0b074cf756224a2a97131207fa891ed8
Source dataset
uspto-grants-2001_02
Patent number
US06184236B2

Reaction notes

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