Boron tribromide → 3-Fluoro-N-(4-fluorophenyl)-4-hydroxy-N-(4-hydroxyphenyl)benzamide

HRID 1486393Notes

Reaction equation

HRID 1486393 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:23]=[CH:24][C:25]=1[O:26]C)[C:5]([N:7]([C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=1)[C:8]1[CH:13]=[CH:12][C:11]([O:14]C)=[CH:10][CH:9]=1)=[O:6].B(Br)(Br)Br>C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([CH:23]=[CH:24][C:25]=1[OH:26])[C:5]([N:7]([C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=1)[C:8]1[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=1)=[O:6]

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 59544195HCID 59544195, compound

Product 1

HCID 468615783-Fluoro-N-(4-fluorophenyl)-4-hydroxy-N-(4-hydroxyphenyl)benzamideYield 81.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Compound 3-fluoro-N-(4-fluorophenyl)-4-methoxy-N-(4-methoxyphenyl)benzamide (2a) (138.0 g, 0.374 mol) was dissolved in dry CH2Cl2 (600 mL) at room temperature under an argon. BBr3 (374.75 g, 1.496 mol) was added dropwise with stirring via a syringe at 0° C. in an ice-bath under an argon. The reaction solution was allowed to stir at room temperature overnight. Then, the solution was poured to 1 L of ice water with stirring. The slurry mixture was stirred at room temperature for 2 hours. The white precipitate was filtered, washed with water (2×100 mL) and dried under vacuum. The CH2Cl2 layer was separated, dried over anhydrous MgSO4 (50 g), filtered and concentrated under reduced pressure to dryness. The white precipitate and residue from CH2Cl2 solution were combined and purified by flash column chromatography (silica gel, CH2Cl2/acetone/MeOH=90/7/3 v/v/v) to give a light tan solid which was recrystallized from hot EtOAc/hexanes solution twice to afford a white crystalline solid, 104.0 g, 81.6% yield. M.p. 110-112° C. MS (ESI) m/z 364.1 [M+Na]+, 1H NMR (DMSO-d6) δ10.14 (bs, 1H), 9.71 (bs, 1H), 7.25-7.11 (m, 5H), 7.05-6.99 (m, 3H), 6.78 (t, J=8.6 Hz, 1H), 6.68 (d, J=8.7 Hz, 2H).

Workup

  1. stirringto stir at room temperature overnight
  2. stirringwith stirring
  3. stirringThe slurry mixture was stirred at room temperature for 2 hours
  4. filtrationThe white precipitate was filtered
  5. washwashed with water (2×100 mL)
  6. customdried under vacuum
  7. customThe CH2Cl2 layer was separated
  8. dry with materialdried over anhydrous MgSO4 (50 g)
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure to dryness
  11. custompurified by flash column chromatography (silica gel, CH2Cl2/acetone/MeOH=90/7/3 v/v/v)
  12. customto give a light tan solid which
  13. customwas recrystallized from hot EtOAc/hexanes solution twice
  14. customto afford a white crystalline solid, 104.0 g, 81.6% yield

Sources & evidence

ORD record
ord-3718c8a60b3d4b28b58081c1ea6789ba
Source dataset
uspto-grants-2016_08
Patent number
US09427418B2

Reaction notes

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