Boron tribromide → 4-[4-(4-Ethyl-5-fluoro-2-hydroxyphenoxy)-3-fluorobenzoyl]piperazin-2-one

HRID 389982Notes

Reaction equation

HRID 389982 reaction equation
[CH2:1]([C:3]1[C:25]([F:26])=[CH:24][C:6]([O:7][C:8]2[CH:22]=[CH:21][C:11]([C:12]([N:14]3[CH2:19][CH2:18][NH:17][C:16](=[O:20])[CH2:15]3)=[O:13])=[CH:10][C:9]=2[F:23])=[C:5]([O:27]C)[CH:4]=1)[CH3:2].B(Br)(Br)Br>ClCCl>[CH2:1]([C:3]1[C:25]([F:26])=[CH:24][C:6]([O:7][C:8]2[CH:22]=[CH:21][C:11]([C:12]([N:14]3[CH2:19][CH2:18][NH:17][C:16](=[O:20])[CH2:15]3)=[O:13])=[CH:10][C:9]=2[F:23])=[C:5]([OH:27])[CH:4]=1)[CH3:2]

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 671162484-[4-(4-Ethyl-5-fluoro-2-methoxyphenoxy)-3-fluorobenzoyl]piperazin-2-one

Product 1

HCID 513473574-[4-(4-Ethyl-5-fluoro-2-hydroxyphenoxy)-3-fluorobenzoyl]piperazin-2-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 4-[4-(4-ethyl-5-fluoro-2-methoxyphenoxy)-3-fluorobenzoyl]piperazin-2-one (38 mg, 0.10 mmol; which may be prepared as described in D3) in dichloromethane (300 μL) under Argon cooled at −30° C. was added dropwise boron tribromide (1M in dichloromethane, 273 μL, 0.27 mmol). The mixture was allowed to come to room temperature and after stirring 20 h, was diluted with dichloromethane. The mixture was quenched carefully at 0° C. with an aqueous saturated solution of ammonium chloride and then diluted with ethyl acetate. The aqueous layer was extracted twice with ethyl acetate and the combined organic phases were washed with brine, dried over sodium sulfate, filtrated and concentrated in vacuo. The residue was purified by preparative thin layer chromatography on silica gel, using dichloromethane/methanol (95:5) as eluent. The title product was obtained as a white solid (32 mg, 86%).

Workup

  1. customto come to room temperature
  2. customThe mixture was quenched carefully at 0° C. with an aqueous saturated solution of ammonium chloride
  3. additiondiluted with ethyl acetate
  4. extractionThe aqueous layer was extracted twice with ethyl acetate
  5. washthe combined organic phases were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltrated
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by preparative thin layer chromatography on silica gel

Sources & evidence

ORD record
ord-86e491e1bd014cb8aadedae65dbce0be
Source dataset
uspto-grants-2013_02
Patent number
US08383621B2

Reaction notes

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