Ethyl chloroformate → 4-Fluoro-2-{2-fluoro-4-[(3-oxopiperazin-1-yl)carbonyl]phenoxy}-5-ethylphenyl ethyl carbonate

HRID 467529Notes

Reaction equation

HRID 467529 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][CH3:28])[CH:4]=1)[CH3:2].[OH-:29].[K+].[CH2:31]([O:33]C(Cl)=O)[CH3:32]>C(#N)C>[C:28](=[O:29])([O:33][CH2:31][CH3:32])[O:27][C:5]1[CH:4]=[C:3]([CH2:1][CH3:2])[C:25]([F:26])=[CH:24][C:6]=1[O:7][C:8]1[CH:22]=[CH:21][C:11]([C:12]([N:14]2[CH2:19][CH2:18][NH:17][C:16](=[O:20])[CH2:15]2)=[O:13])=[CH:10][C:9]=1[F:23]

Participants

5

Reactant 3

HCID 10928Ethyl chloroformateHCID 14797Potassium HydroxideHCID 671162484-[4-(4-Ethyl-5-fluoro-2-methoxyphenoxy)-3-fluorobenzoyl]piperazin-2-one

Product 1

HCID 513565044-Fluoro-2-{2-fluoro-4-[(3-oxopiperazin-1-yl)carbonyl]phenoxy}-5-ethylphenyl ethyl carbonate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 4-[4-(4-ethyl-5-fluoro-2-hydroxyphenoxy)-3-fluorobenzoyl]piperazin-2-one (20 mg, 0.053 mmol; which may be prepared as described in D3) in acetonitrile (550 μL) was added KOH (3 mg, 0.053 mmol) followed by ethylchlorocarbonate (6 μL, 0.058 mmol). After 1 hour at room temperature, the mixture was quenched with water. The aqueous layer was extracted twice with ethyl acetate. The organic phase was dried over sodium sulphate, filtered and concentrated under vacuum. 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 (11 mg, 46%).

Workup

  1. customthe mixture was quenched with water
  2. extractionThe aqueous layer was extracted twice with ethyl acetate
  3. dry with materialThe organic phase was dried over sodium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. customThe residue was purified by preparative thin layer chromatography on silica gel

Sources & evidence

ORD record
ord-96d7f076e03940668dc83281bdf32e1e
Source dataset
uspto-grants-2014_01
Patent number
US08623865B2

Reaction notes

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