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

HRID 1513852Notes

Reaction equation

HRID 1513852 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[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[O: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(Cl)Cl>[ClH:47].[F:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[C:3]=1[C:9]1[C:10]([O: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 113407861-(2-{4-[2-(2,6-Difluoro-phenyl)-6-methoxy-naphthalen-1-yloxy]-phenoxy}-ethyl)-piperidineHCID 21906603Chloroform isopropyl alcohol

Product 1

HCID 670047526-(2,6-Difluoro-phenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-phenoxy]-naphthalen-2-ol hydrochlorideYield 48%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Dissolve 1-(2-{4-[2-(2,6-difluoro-phenyl)-6-methoxy-naphthalen-1-yloxy]-phenoxy}-ethyl)-piperidine (300 mg., 0.61 mmoles) in 20 ml methylene chloride and chill in ice. To this add 2.0 ml of boron tribromide with swirling and allow to warm to room temperature. Pour this mixture into a two-phase mixture consisting of saturated sodium bicarbonate and a 3/1 mixture of chloroform/isopropanol. Wash the organic layer with brine and dry over 3A molecular sieves. Purify further using reverse phase chromatography to give 138 mg of the title compound (48%). Convert to hydrochloride salt and lyophilize. 1H-NMR (CDCl3, 300 MHz) δ7.92 (d, J=9.0 Hz, 1H); 7.59 (d, J=8.4 Hz, 1H); 7.35 (d, J=8.4 Hz, 1H); 7.20-7.17 (m, 2H); 7.03 (dd, J=9.0, 2.1 Hz, 1H); 6.85-6.80 (m, 2H); 6.52 (s, 4H); 3.95 (t, J=5.7 Hz, 2H); 2.73 (t, J=6.0 Hz, 2H); 2.52-2.52 (m, 4H); 1.64-1.59 (m, 4H); 1.46-1.44 (m, 2H).

Workup

  1. temperaturechill in ice
  2. additionPour this mixture into a two-phase mixture
  3. washWash the organic layer with brine
  4. dry with materialdry over 3A molecular sieves
  5. customPurify further

Sources & evidence

ORD record
ord-a1cfe67b6a7d4953af91203b9b537e24
Source dataset
uspto-grants-2012_07
Patent number
US08217032B2

Reaction notes

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