Ethyl Acetate → 1-{2-[4-(2-Benzyloxy-6-methoxy-naphthalen-1-yloxy)-phenoxy]-ethyl}-piperidine

HRID 445198Notes

Reaction equation

HRID 445198 reaction equation
[CH2:1]([O:8][C:9]1[CH:18]=[CH:17][C:16]2[C:11](=[CH:12][CH:13]=[C:14]([O:19][CH3:20])[CH:15]=2)[C:10]=1Br)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N:22]1([CH2:28][CH2:29][O:30][C:31]2[CH:36]=[CH:35][C:34]([OH:37])=[CH:33][CH:32]=2)[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1.C(=O)([O-])[O-].[Cs+].[Cs+].C(OCC)(=O)C>C1(C)C=CC=CC=1>[CH2:1]([O:8][C:9]1[CH:18]=[CH:17][C:16]2[C:11](=[CH:12][CH:13]=[C:14]([O:19][CH3:20])[CH:15]=2)[C:10]=1[O:37][C:34]1[CH:33]=[CH:32][C:31]([O:30][CH2:29][CH2:28][N:22]2[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]2)=[CH:36][CH:35]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 106090214-[2-(Piperidin-1-yl)ethoxy]phenolHCID 117029082-Benzyloxy-1-bromo-6-methoxy-naphthalene

Product 1

HCID 116774331-{2-[4-(2-Benzyloxy-6-methoxy-naphthalen-1-yloxy)-phenoxy]-ethyl}-piperidineYield 30%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
174 °C

Procedure

Combine toluene (200 mL), 2-benzyloxy-1-bromo-6-methoxy-naphthalene (30 g, 87.4 mmol), 4-(2-piperidin-1-yl-ethoxy)phenol (23.2 g, 105 mmol) and cesium carbonate (34.4 g, 105 mmol). Heat the mixture to reflux. Remove a portion of the toluene by distillation (100 mL). Add ethyl acetate (390 mg, 4.37 mmol) and copper triflate benzene complex (2.20 g, 4.37 mmol) to the reaction mixture and stir for 5 minutes. Remove the solvent by distillation and heat the resulting residue to 174° C. for 1.5 hours. Dissolve the residue in a mixture of ethyl acetate (200 mL) and aqueous HCl (1 N, 90 mL). Separate and concentrate the organic solution to a residue. Purify the residue by silica gel chromatography to give 1-{2-[4-(2-benzyloxy-6-methoxy-naphthalen-1-yloxy)-phenoxy]-ethyl}-piperidine (12.4 g, 26.2 mmol).

Workup

  1. temperatureHeat the mixture
  2. temperatureto reflux
  3. customRemove a portion of the toluene
  4. distillationby distillation (100 mL)
  5. customRemove the solvent
  6. distillationby distillation
  7. dissolutionDissolve the residue
  8. additionin a mixture of ethyl acetate (200 mL) and aqueous HCl (1 N, 90 mL)
  9. customSeparate
  10. concentrationconcentrate the organic solution to a residue
  11. customPurify the residue by silica gel chromatography

Sources & evidence

ORD record
ord-322eec60e91b4c408add059a6cdbde0e
Source dataset
uspto-grants-2013_07
Patent number
US08476300B2

Reaction notes

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