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

HRID 389995Notes

Reaction equation

HRID 389995 reaction equation
B(Br)(Br)Br.[CH2:5]([C:7]1[C:29]([F:30])=[CH:28][C:10]([O:11][C:12]2[CH:26]=[CH:25][C:15]([C:16]([N:18]3[CH2:23][CH2:22][NH:21][C:20](=[O:24])[CH2:19]3)=[O:17])=[CH:14][C:13]=2[F:27])=[C:9]([O:31]C)[CH:8]=1)[CH3:6].O>ClCCl>[CH2:5]([C:7]1[C:29]([F:30])=[CH:28][C:10]([O:11][C:12]2[CH:26]=[CH:25][C:15]([C:16]([N:18]3[CH2:23][CH2:22][NH:21][C:20](=[O:24])[CH2:19]3)=[O:17])=[CH:14][C:13]=2[F:27])=[C:9]([OH:31])[CH:8]=1)[CH3:6]

Participants

5

Reactant 3

HCID 962WaterHCID 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

A commercial solution of boron tribromide (1N in DCM, 3.5 mL, 3.46 mmol) was added to a solution of 4-[4-(4-ethyl-5-fluoro-2-methoxyphenoxy)-3-fluorobenzoy] piperazin-2-one (which may be prepared in accordance with the experimental described in Example 5, step 1; 500 mg, 1.28 mmol) in dichloromethane (4.3 mL) placed under argon at −30° C. The reaction mixture was stirred at room temperature for 36 hours then diluted by addition of dichloromethane (20 mL) and water (20 mL). After separation, the aqueous layer was extracted with dichloromethane (2×20 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/acetone (80:20) as eluent. The title product was obtained as a beige solid (440 mg, 92%).

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 (2×20 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-6551d6d96221433fa0f82842a13d9bb8
Source dataset
uspto-grants-2013_02
Patent number
US08383621B2

Reaction notes

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