Boron tribromide → [4-(2-Azepan-1-yl-ethoxy)-phenyl]-[2-(2,6-difluoro-phenyl)-6-hydroxy-naphthalen-1-yl]-methanone

HRID 1513904Notes

Reaction equation

HRID 1513904 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[C:36]([F:37])=[CH:35][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[C:32]([F:38])=[CH:33][CH:34]=[CH:35][C:36]=3[F:37])=[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 57552543[4-(2-Azepan-1-yl-ethoxy)-phenyl]-[2-(2,6-difluorophenyl)-6-methoxy-naphthalen-1-yl]-methanone

Product 1

HCID 67004735[4-(2-Azepan-1-yl-ethoxy)-phenyl]-[2-(2,6-difluoro-phenyl)-6-hydroxy-naphthalen-1-yl]-methanoneYield 54%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Convert [4-(2-azepan-1-yl-ethoxy)-phenyl]-[2-(2,6-difluoro-phenyl)-6-methoxy-naphthalen-1-yl]-methanone (2.5 g, 4.8 mmol) into the hydrochloride salt and charge a flask with the solid salt. Dissolve the material in 200 mL methylene chloride and chill in ice. Add to this mixture boron tribromide (5.0 mL, 53.0 mmol) while swirling. Stir the reaction at room temperature for one hour and pour into a two phase system of saturated sodium bicarbonate and an organic layer consisting of a 3/1 mixture of chloroform/isopropanol. Shake to extract the product, separate the organic layer, dry over 3 Å molecular sieves and evaporate the solvent under vacuum. Purify on a silica gel column eluting with a 0-10% methanol/methylene chloride gradient to give 1.3 g (54%) of the title compound: 1H-NMR (CDCl3, 400 MHz) δ 7.79-7.74 (d, 1H); 7.58 (d, J=8.4 Hz, 2H); 7.50 (d, J=8.8 Hz, 1H); 7.33-7.30 (d, 1H); 7.17 (d, J=2.4 Hz, 1H); 7.16-7.08 (m, 1H); 6.99-6.95 (dd, 1H); 6.77-6.73 (m, 2H); 6.68 (d, J=9.2 Hz, 2H); 4.11 (t, J=6.0 Hz, 2H); 3.05-2.99 (t, 2H); 2.90-2.84 (m, 4H); 1.71-1.71 (m, 4H); 1.63-1.60 (m, 4H).

Workup

  1. temperaturechill in ice
  2. customthe reaction at room temperature for one hour
  3. extractionShake to extract the product
  4. customseparate the organic layer
  5. customdry over 3 Å molecular sieves
  6. customevaporate the solvent under vacuum
  7. customPurify on a silica gel column
  8. washeluting with a 0-10% methanol/methylene chloride gradient

Sources & evidence

ORD record
ord-5a96e6215dab49738b2fecd108ddaf7d
Source dataset
uspto-grants-2012_07
Patent number
US08217032B2

Reaction notes

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