3-Aminobenzamide → 3-[2-(4-Bromo-2-chloro-phenoxy)acetyl-amino]-benzamide

HRID 1945388

Reaktionsgleichung

Reaktionsgleichung von HRID 1945388
[Br:1][C:2]1[CH:12]=[CH:11][C:5]([O:6][CH2:7][C:8]([OH:10])=O)=[C:4]([Cl:13])[CH:3]=1.[NH2:14][C:15]1[CH:16]=[C:17]([CH:21]=[CH:22][CH:23]=1)[C:18]([NH2:20])=[O:19].Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C=O)C>[Br:1][C:2]1[CH:12]=[CH:11][C:5]([O:6][CH2:7][C:8]([NH:14][C:15]2[CH:16]=[C:17]([CH:21]=[CH:22][CH:23]=2)[C:18]([NH2:20])=[O:19])=[O:10])=[C:4]([Cl:13])[CH:3]=1

Komponenten

7

Edukt 5

HCID 16453-AminobenzamideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 6931572-(4-Bromo-2-chlorophenoxy)acetic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Produkt 1

HCID 248111063-[2-(4-Bromo-2-chloro-phenoxy)acetyl-amino]-benzamideAusbeute 94,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A mixture of 4-bromo-2-chloro-phenol (2.0 g, 9.64 mmol) and anhydrous potassium carbonate (4.0 g, 28.92 mmol) in dry DMF (30 ml) was heated at 60° C. for 1 h under Ar atmosphere. The mixture was then cooled to room temperature and ethyl chloroacetate (1.24 ml, 11.57 mmol) was added through septum using syringe. The mixture was stirred overnight at room temperature and poured into water with stirring. Stirring continued for 10 min, and then partitioned between ethyl acetate and water. The organic phase washed with brine, dried (anhydrous MgSO4), and concentrated. The residue was purified by silica gel column chromatography (n-Hexane:Ethyl acetate:MeOH=15:3:1) to give (4-Bromo-2-chloro-phenoxy)-acetic acid ethyl ester as a colorless oil (2.98 (2.83) g, >100% yield). To (4-bromo-2-chloro-phenoxy)-acetic acid (132.8 mg, 0.5 mmol), 3-amino-benzamide (102.2 mg, 0.75 mmol), N-(3-dimethylaminopropyl)-N′-ethyl carbodiimide HCl (EDC) (143.8 mg, 0.75 mmol) and 1-hydroxybenzotriazole (HOBt) (101.4 mg, 0.75 mmol) in DMF (5 ml) was added N,N-diisopropylethylamine, redistilled (DIPEA) (0.13 ml, 0.75 mmol). The mixture was stirred overnight, and then partitioned between ethyl acetate and water. The organic phase was washed with brine, dried (MgSO4 anh), and concentrated. The residue was purified by silica gel flash column chromatography (CH2CH2:MeOH=10:1) to give 3-[2-(4-bromo-2-chloro-phenoxy)acetyl-amino]-benzamide as a white solid (181.4 mg, 94.6% yield).

Aufarbeitung

  1. distillationredistilled (DIPEA) (0.13 ml, 0.75 mmol)
  2. custompartitioned between ethyl acetate and water
  3. washThe organic phase was washed with brine
  4. dry with materialdried (MgSO4 anh)
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel flash column chromatography (CH2CH2:MeOH=10:1)

Quellen und Nachweise

ORD-Eintrag
ord-25887fe2ee544fb98746a2423fa32c33
Quelldatensatz
uspto-grants-2013_03
Patentnummer
US08394799B2

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