Water → [4-(2-Azepan-1-yl-ethoxy)-phenyl]-(2-hydroxy-6-methoxy-naphthalen-1-yl)-methanone

HRID 1513893Notes

Reaction equation

HRID 1513893 reaction equation
[N:1]1([CH2:8][CH2:9][O:10][C:11]2[CH:19]=[CH:18][C:14]([C:15](Cl)=[O:16])=[CH:13][CH:12]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:20][O:21][C:22]1[CH:31]=[CH:30][C:29]2[C:24](=[CH:25][CH:26]=[C:27]([O:32]C)[CH:28]=2)[CH:23]=1.[Cl-].[Cl-].[Cl-].[Al+3].O>ClCCl>[N:1]1([CH2:8][CH2:9][O:10][C:11]2[CH:19]=[CH:18][C:14]([C:15]([C:28]3[C:29]4[C:24](=[CH:23][C:22]([O:21][CH3:20])=[CH:31][CH:30]=4)[CH:25]=[CH:26][C:27]=3[OH:32])=[O:16])=[CH:13][CH:12]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 962WaterHCID 796272,6-DimethoxynaphthaleneHCID 6451240Aluminum(III) ChlorideHCID 227430554-(2-Azepan-1-yl-ethoxy)-benzoyl chloride

Product 1

HCID 67004584[4-(2-Azepan-1-yl-ethoxy)-phenyl]-(2-hydroxy-6-methoxy-naphthalen-1-yl)-methanoneYield 85.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-5 °C

Procedure

Dissolve 4-(2-azepan-1-yl-ethoxy)-benzoyl chloride (79.4 g, 249 mmol) and 2,6-dimethoxynaphthalene (37.8 g, 201 mmol) in dichloromethane (800 ml). Cool to −5° C. and add aluminum trichloride (134 g, 1 mol). Warm to room temperature and stir overnight. Add chilled water (1.5 L) and stir vigorously for 1 hour. Decant the mixture away from the residue and separate organic. Wash the aqueous layer with dichloromethane (500 mL). Combine with residue from the reaction vessel and wash with saturated aqueous sodium bicarbonate (1 L). Separate the organic after prolonged stirring (2 hours) and wash the aqueous layer with dichloromethane (300 mL). Combine the organic layers and add Darco (30 g), silica gel (30 g), and magnesium sulfate. Filter and concentrate in vacuo to give 72.4 g of [4-(2-azepan-1-yl-ethoxy)-phenyl]-(2-hydroxy-6-methoxy-naphthalen-1-yl)-methanone (73%).

Workup

  1. temperatureWarm to room temperature
  2. additionAdd
  3. stirringstir vigorously for 1 hour
  4. customDecant the mixture away from the residue
  5. customseparate organic
  6. washWash the aqueous layer with dichloromethane (500 mL)
  7. washCombine with residue from the reaction vessel and wash with saturated aqueous sodium bicarbonate (1 L)
  8. customSeparate the organic
  9. stirringafter prolonged stirring (2 hours)
  10. washwash the aqueous layer with dichloromethane (300 mL)
  11. additionCombine the organic layers and add Darco (30 g), silica gel (30 g), and magnesium sulfate
  12. filtrationFilter
  13. concentrationconcentrate in vacuo

Sources & evidence

ORD record
ord-c186b5165a2843f0a1f2cb85c2ed2f99
Source dataset
uspto-grants-2012_07
Patent number
US08217032B2

Reaction notes

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