Boron tribromide → 6-(2,5-Difluoro-phenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-naphthalen-2-ol hydrochloride

HRID 1513912Notes

Reaction equation

HRID 1513912 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9]1[CH:18]=[CH:17][C:16]2[C:11](=[CH:12][CH:13]=[C:14]([O:19]C)[CH:15]=2)[C:10]=1[CH2:21][C:22]1[CH:36]=[CH:35][C:25]([O:26][CH2:27][CH2:28][N:29]2[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]2)=[CH:24][CH:23]=1.B(Br)(Br)Br.C(=O)(O)[O-].[Na+].C(Cl)(Cl)[Cl:47].C(O)(C)C>C(#N)C>[ClH:47].[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9]1[C:10]([CH2:21][C:22]2[CH:36]=[CH:35][C:25]([O:26][CH2:27][CH2:28][N:29]3[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34]3)=[CH:24][CH:23]=2)=[C:11]2[C:16](=[CH:17][CH:18]=1)[CH:15]=[C:14]([OH:19])[CH:13]=[CH:12]2

Participants

6

Reactant 4

HCID 25134Boron tribromideHCID 516892Sodium BicarbonateHCID 21906603Chloroform isopropyl alcoholHCID 575525571-(2-{4-[2-(2,5-Difluoro-phenyl)-6-methoxy-naphthalen-1-ylmethyl]-phenoxy}-ethyl)-piperidine

Product 1

HCID 670041636-(2,5-Difluoro-phenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-naphthalen-2-ol hydrochlorideYield 82%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Dissolve 1-(2-{4-[2-(2,5-difluoro-phenyl)-6-methoxy-naphthalen-1-ylmethyl]-phenoxy}-ethyl)-piperidine in 20 mL acetonitrile and chill in an ice bath. Add 1.5 mL of boron tribromide with swirling and allow to warm to room temperature. Pour this mixture into a two-phase mixture of saturated sodium bicarbonate solution and a 3/1 mixture of chloroform/isopropanol. Wash the organic layer with water and dry over 3 Å molecular sieves. Concentrate the organic layer and purify on a silica gel column, eluting with a 0-10% methanol/methylene chloride gradient. Evaporate the solvent and convert the compound to the salt with HCl to give 369 mg (82%) of the title compound: 1H-NMR (CDCl3, 300 MHz) δ7.77 (d, J=8.7 Hz, 1H); 7.61 (d, J=8.1 Hz, 1H); 7.28-7.25 (m, 1H); 7.11-6.94 (m, 4H); 6.89-6.83 (m, 1H); 6.74 (d, J=8.7 Hz, 2H); 6.57-6.54 (m, 2H); 4.31-4.10 (d, 2H); 4.04 (t, J=6.0 Hz, 2H); 2.80-2.80 (m, 2H); 2.59-2.59 (m, 4H); 1.68-1.65 (m, 4H); 1.48-1.46 (m, 2H).

Workup

  1. temperaturechill in an ice bath
  2. additionPour this mixture
  3. washWash the organic layer with water
  4. customdry over 3 Å molecular sieves
  5. concentrationConcentrate the organic layer
  6. custompurify on a silica gel column
  7. washeluting with a 0-10% methanol/methylene chloride gradient
  8. customEvaporate the solvent

Sources & evidence

ORD record
ord-7279ba071933407bb6dec48308239df5
Source dataset
uspto-grants-2012_07
Patent number
US08217032B2

Reaction notes

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