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

HRID 748868Notes

Reaction equation

HRID 748868 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 (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 organics to a residue. Column chromatograph the residue to give 12.4 g of 1-{2-[4-(2-benzyloxy-6-methoxy-naphthalen-1-yloxy)-phenoxy]-ethyl}-piperidine (30%).

Workup

  1. temperatureto reflux
  2. customRemove a portion of the toluene (100 mL)
  3. customRemove the solvent
  4. distillationby distillation
  5. dissolutionDissolve the residue
  6. additionin a mixture of ethyl acetate (200 mL) and aqueous HCl (1 N, 90 mL)
  7. customSeparate
  8. concentrationconcentrate the organics to a residue

Sources & evidence

ORD record
ord-4697cdbda4124202a55fb1f24f86b98d
Source dataset
uspto-grants-2008_07
Patent number
US07399867B2

Reaction notes

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