Hydrochloric Acid → 4-[4-(4-Ethyl-5-fluoro-2-methoxyphenoxy)-3-fluorobenzoyl]piperazin-2-one

HRID 389981Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 389981
[CH2:1]([C:3]1[C:19]([F:20])=[CH:18][C:6]([O:7][C:8]2[CH:16]=[CH:15][C:11]([C:12]([OH:14])=O)=[CH:10][C:9]=2[F:17])=[C:5]([O:21][CH3:22])[CH:4]=1)[CH3:2].C(Cl)(=O)C(Cl)=O.[NH:29]1[CH2:34][CH2:33][NH:32][CH2:31][C:30]1=[O:35].C(N(C(C)C)CC)(C)C.Cl>ClCCl.CN(C)C=O>[CH2:1]([C:3]1[C:19]([F:20])=[CH:18][C:6]([O:7][C:8]2[CH:16]=[CH:15][C:11]([C:12]([N:32]3[CH2:33][CH2:34][NH:29][C:30](=[O:35])[CH2:31]3)=[O:14])=[CH:10][C:9]=2[F:17])=[C:5]([O:21][CH3:22])[CH:4]=1)[CH3:2]

Komponenten

8

Edukt 5

HCID 313Hydrochloric AcidHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 231360Piperazin-2-oneHCID 671160464-(4-Ethyl-5-fluoro-2-methoxyphenoxy)-3-fluorobenzoic acid

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a solution of 4-(4-ethyl-5-fluoro-2-methoxyphenoxy)-3-fluorobenzoic acid (55 mg, 0.18 mmol; which may be prepared as described in D2) in dichloromethane (1.8 mL) under Argon cooled at 0° C. were added oxalyl chloride (2M in dichloromethane, 135 μL, 0.27 mmol) and a drop of N,N-dimethylformamide. The mixture was allowed to come to room temperature over 2 hours, and then piperazin-2-one (20 mg, 0.20 mmol) followed by diisopropylethylamine (93 μL, 0.53 mmol) were added. The reaction mixture was cooled to 0° C. and a solution of 1N HCl was added. After stirring a few minutes, dichloromethane was added and the aqueous layer (pH 7) was extracted twice with dichloromethane. The combined organic phases were 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 yellow oil (38 mg, 55%).

Aufarbeitung

  1. additionwere added
  2. extractionthe aqueous layer (pH 7) was extracted twice with dichloromethane
  3. dry with materialThe combined organic phases were dried over sodium sulfate
  4. filtrationfiltrated
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by preparative thin layer chromatography on silica gel

Quellen und Nachweise

ORD-Eintrag
ord-30e37a3c40f5432298040e3e61dc07eb
Quelldatensatz
uspto-grants-2013_02
Patentnummer
US08383621B2

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