Boron tribromide → [4-(2-Azepan-1-yl-ethoxy)-phenyl][2-(2,5-difluorophenyl)-6-hydroxynaphthalen-1-yl]-methanone

HRID 1513906Notes

Reaction equation

HRID 1513906 reaction equation
[N:1]1([CH2:8][CH2:9][O:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]([C:19]3[C:28]4[C:23](=[CH:24][C:25]([O:29]C)=[CH:26][CH:27]=4)[CH:22]=[CH:21][C:20]=3[C:31]3[CH:36]=[C:35]([F:37])[CH:34]=[CH:33][C:32]=3[F:38])=[O:18])=[CH:13][CH:12]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.B(Br)(Br)Br.C(=O)(O)[O-].[Na+].C(Cl)(Cl)Cl.C(O)(C)C>C(Cl)Cl>[N:1]1([CH2:8][CH2:9][O:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]([C:19]3[C:28]4[C:23](=[CH:24][C:25]([OH:29])=[CH:26][CH:27]=4)[CH:22]=[CH:21][C:20]=3[C:31]3[CH:36]=[C:35]([F:37])[CH:34]=[CH:33][C:32]=3[F:38])=[O:18])=[CH:13][CH:12]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 25134Boron tribromideHCID 516892Sodium BicarbonateHCID 21906603Chloroform isopropyl alcoholHCID 57552524[4-(2-Azepan-1-yl-ethoxy)-phenyl]-[2-(2,5-difluoro-phenyl)-6-methoxy-naphthalen-1-yl]-methanone

Product 1

HCID 67004614[4-(2-Azepan-1-yl-ethoxy)-phenyl][2-(2,5-difluorophenyl)-6-hydroxynaphthalen-1-yl]-methanoneYield 46.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Dissolve [4-(2-azepan-1-yl-ethoxy)-phenyl]-[2-(2,5-difluoro-phenyl)-6-methoxy-naphthalen-1-yl]-methanone (1.74 g, 3.37 mmol) in 20 mL methylene chloride and chill in ice. Add to this solution 2.0 mL of boron tribromide (5.3 g, 21.2 mmol) and allow to come to room temperature. Pour into a two phase solution of saturated sodium bicarbonate and 3/1 chloroform/isopropanol. Separate the organic layer, wash with water and dry over 3A sieves. Evaporate the solvent and purify on a silica gel column eluting with a 0-10% methanol/methylene chloride gradient. Evaporate the solvent to give 780 mg (46%) of the title compound: 1H-NMR (CDCl3, 300 MHz) δ 7.79 (d, J=8.7 Hz, 1H); 7.60-7.55 (m, 3H); 7.41 (dd, J=8.7, 1.8 Hz, 1H); 726-7.21 (m, 1H); 7.04-6.82 (m, 4H); 6.71-6.68 (m, 2H); 4.14-4.14 (m, 2H): 3.03-2.97 (m, 2H); 2.95-2.88 (m, 4H); 1.73-1.58 (m, 8H).

Workup

  1. temperaturechill in ice
  2. customto come to room temperature
  3. customSeparate the organic layer
  4. washwash with water
  5. dry with materialdry over 3A sieves
  6. customEvaporate the solvent
  7. custompurify on a silica gel column
  8. washeluting with a 0-10% methanol/methylene chloride gradient
  9. customEvaporate the solvent

Sources & evidence

ORD record
ord-3c342d8197fa484cba651b832f362a25
Source dataset
uspto-grants-2012_07
Patent number
US08217032B2

Reaction notes

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