Boron tribromide → 4-[4-(4-Ethyl-5-fluoro-2-hydroxyphenoxy)-3-fluorobenzoyl]piperazine-2,6-dione

HRID 389989Notes

Reaction equation

HRID 389989 reaction equation
B(Br)(Br)Br.[CH2:5]([C:7]1[C:30]([F:31])=[CH:29][C:10]([O:11][C:12]2[CH:27]=[CH:26][C:15]([C:16]([N:18]3[CH2:23][C:22](=[O:24])[NH:21][C:20](=[O:25])[CH2:19]3)=[O:17])=[CH:14][C:13]=2[F:28])=[C:9]([O:32]C)[CH:8]=1)[CH3:6].[Cl-].[NH4+]>ClCCl>[CH2:5]([C:7]1[C:30]([F:31])=[CH:29][C:10]([O:11][C:12]2[CH:27]=[CH:26][C:15]([C:16]([N:18]3[CH2:19][C:20](=[O:25])[NH:21][C:22](=[O:24])[CH2:23]3)=[O:17])=[CH:14][C:13]=2[F:28])=[C:9]([OH:32])[CH:8]=1)[CH3:6]

Participants

5

Reactant 3

HCID 25134Boron tribromideHCID 25517Ammonium ChlorideHCID 671160884-[4-(4-Ethyl-5-fluoro-2-methoxyphenoxy)-3-fluorobenzoyl]piperazine-2,6-dione

Product 1

HCID 513565024-[4-(4-Ethyl-5-fluoro-2-hydroxyphenoxy)-3-fluorobenzoyl]piperazine-2,6-dione

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A commercial solution of boron tribromide (1N in DCM, 0.4 mL, 0.4 mmol) was added to a solution of 4-[4-(4-ethyl-5-fluoro-2-methoxyphenoxy)-3-fluorobenzoyl]piperazine-2,6-dione (which may be prepared in accordance with the experimental described in Example 4, step 5; 60 mg, 0.15 mmol) in dichloromethane (0.5 mL) placed under argon at −30° C. The reaction mixture was stirred at room temperature overnight and then diluted by addition of dichloromethane (10 mL) and a saturated solution of ammonium chloride (10 mL). After separation, the aqueous layer was extracted with dichloromethane (2×10 mL). The combined organic phases were dried over sodium sulfate, filtered and concentrated under vacuum. The residue was purified by chromatography on silica gel, using dichloromethane/methanol (98:2) as eluent. The title product was obtained as a white solid (35 mg, 60%).

Workup

  1. custommay be prepared in accordance with the
  2. customplaced under argon at −30° C
  3. customAfter separation
  4. extractionthe aqueous layer was extracted with dichloromethane (2×10 mL)
  5. dry with materialThe combined organic phases were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customThe residue was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-0db4f30d96d84b5ab3270f52ffea0500
Source dataset
uspto-grants-2013_02
Patent number
US08383621B2

Reaction notes

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