Potassium Carbonate → 1-{2-[4-(2-Benzyloxy-6-methoxy-naphthalen-1-yloxy)-phenoxy]ethyl}-azepane

HRID 1513869Notes

Reaction equation

HRID 1513869 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([CH2:29][CH2:30][O:31][C:32]2[CH:37]=[CH:36][C:35]([OH:38])=[CH:34][CH:33]=2)[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1.C(=O)([O-])[O-].[K+].[K+]>[Cu].N1C=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:38][C:35]1[CH:34]=[CH:33][C:32]([O:31][CH2:30][CH2:29][N:22]2[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]2)=[CH:37][CH:36]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 117029082-Benzyloxy-1-bromo-6-methoxy-naphthaleneHCID 670048004-(2-Azepan-1-yl-ethoxy)-phenol

Product 1

HCID 670044981-{2-[4-(2-Benzyloxy-6-methoxy-naphthalen-1-yloxy)-phenoxy]ethyl}-azepaneYield 43%

Reagents, catalysts & solvents 2

HCID 23978CopperCatalystHCID 1049PyridineSolvent

Procedure

Combine 2-benzyloxy-1-bromo-6-methoxy-naphthalene (31 g, 90 mmol), 4-(2-azepan-1-yl-ethoxy)-phenol (31 g, 132 mmol), copper bronze (12 g, 189 mmol), potassium carbonate (25 g, 181 mmol) and pyridine (400 ml). Heat the reaction mixture to reflux for 85 hours. Coot and filter the residue with celite and elute with methanol and methylene chloride (500 mL, V/V=1:5). Evaporate solvent under reduced pressure and chromatograph the residue on a silica gel column eluting the material with a step gradient of methanol/dichloromethane (0 to 10%) to get 19 g (43%) of 1-{2-[4-(2-benzyloxy-6-methoxy-naphthalen-1-yloxy)-phenoxy]ethyl}-azepane.

Workup

  1. temperatureHeat the reaction mixture
  2. temperatureto reflux for 85 hours
  3. filtrationCoot and filter the residue with celite
  4. washelute with methanol and methylene chloride (500 mL, V/V=1:5)
  5. washEvaporate solvent under reduced pressure and chromatograph the residue on a silica gel column eluting the material with a step gradient of methanol/dichloromethane (0 to 10%)

Sources & evidence

ORD record
ord-02b02fa56e4f45a483d63a7fbd6ad477
Source dataset
uspto-grants-2012_07
Patent number
US08217032B2

Reaction notes

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