Boron tribromide → HCID 67004441, compound

HRID 1513917Notes

Reaction equation

HRID 1513917 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:17]=[CH:16][C:15]3[C:10](=[CH:11][CH:12]=[C:13]([O:18]C)[CH:14]=3)[C:9]=2[CH2:20][C:21]2[CH:35]=[CH:34][C:24]([O:25][CH2:26][CH2:27][N:28]3[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]3)=[CH:23][CH:22]=2)[CH:5]=[CH:6][CH:7]=1.B(Br)(Br)Br.C(=O)(O)[O-].[Na+].C(Cl)(Cl)[Cl:46].C(O)(C)C>C(Cl)Cl>[ClH:46].[F:1][C:2]1[CH:3]=[C:4]([C:8]2[C:9]([CH2:20][C:21]3[CH:35]=[CH:34][C:24]([O:25][CH2:26][CH2:27][N:28]4[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]4)=[CH:23][CH:22]=3)=[C:10]3[C:15](=[CH:16][CH:17]=2)[CH:14]=[C:13]([OH:18])[CH:12]=[CH:11]3)[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 25134Boron tribromideHCID 516892Sodium BicarbonateHCID 18182607HCID 18182607, compoundHCID 21906603Chloroform isopropyl alcohol

Product 1

HCID 67004441HCID 67004441, compoundYield 57%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Charge a flask with 1-(2-{4-[2-(3-fluorophenyl)-6-methoxy-naphthalen-1-ylmethyl]-phenoxy}-ethyl)-piperidine (1.1 g, 2.3 mmol) dissolved in 250 mL methylene chloride and chill in ice. Add 6.0 mL of neat boron tribromide in portions with stirring and stir the reaction in ice for one hour then at room temperature for 2 hours. Pour the reaction into a two-phase mixture consisting of saturated sodium bicarbonate and an organic phase of 3/1 chloroform/isopropanol. Extract the compound into the organic phase using a separatory funnel, separate the phases and dry the organic layer over 3 Å molecular sieves. Evaporate and purify on a silica column eluting with 3% methanol/methylene chloride. Convert to the hydrochloride salt and lyophilize to yield 650 mg (57%) of the title compound: 1H-NMR (data reported for the free base) (CDCl3, 400 MHz) δ 7.73 (d, J=9.6 Hz, 1H); 7.61 (d, J=8.0 Hz, 1H); 7.32-7.30 (m, 1H); 7.28-7.24 (m, H); 7.15 (d, J=2.0 Hz, 1H); 7.04-6.94 (m, 4H); 6.79 (d, J=8.4 Hz, 2H); 6.62-6.59 (m, 2H); 4.28 (s, 2H); 4.13 (t, J=5.6 Hz, 2H); 2.92-2.92 (m, 2H); 2.72-2.64 (m, 4H); 1.74 (d, J=4.8 Hz, 4H); 1.51-1.51 (m, 2H).

Workup

  1. temperaturechill in ice
  2. stirringstir
  3. customthe reaction in ice for one hour
  4. additionPour
  5. customthe reaction into a two-phase mixture
  6. extractionExtract the compound into the organic phase
  7. customseparate the phases
  8. customdry the organic layer over 3 Å molecular sieves
  9. customEvaporate
  10. custompurify on a silica column
  11. washeluting with 3% methanol/methylene chloride

Sources & evidence

ORD record
ord-e13fa8498b63462bb7fa08e2d828d7c2
Source dataset
uspto-grants-2012_07
Patent number
US08217032B2

Reaction notes

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