Hydrochloric Acid → HCID 117761114, Verbindung

HRID 523271

Reaktionsgleichung

Reaktionsgleichung von HRID 523271
[Br:1][C:2]1[C:3]([Cl:9])=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].C[Al](C)C.[F:14][C:15]1[C:20]2[NH:21]C(=O)[O:23][C:24](=O)[C:19]=2[CH:18]=[CH:17][CH:16]=1.Cl>C1(C)C=CC=CC=1>[NH2:21][C:20]1[C:15]([F:14])=[CH:16][CH:17]=[CH:18][C:19]=1[C:24]([NH:5][C:4]1[CH:6]=[CH:7][CH:8]=[C:2]([Br:1])[C:3]=1[Cl:9])=[O:23]

Komponenten

6

Edukt 4

HCID 313Hydrochloric AcidHCID 189585Benzenamine, ar-bromo-ar-chloro-HCID 105353933-Fluoroisatoic anhydrideHCID 16682925Trimethylaluminum

Produkt 1

HCID 117761114HCID 117761114, VerbindungAusbeute 35 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1140TolueneLösungsmittel2×

Versuchsvorschrift

A mixture of 3-bromo-2-chloroaniline [prepared according to the procedure described in U.S. Pat. No. 8,242,260] (600 mg, 2.91 mmol) and toluene (10 mL) was cooled to 0° C. and slowly treated with 2 M trimethylaluminum in toluene (2.47 mL, 4.94 mmol). The mixture was allowed to warm to room temperature and stirred for 15 min. The mixture was treated with 8-fluoro-1H-benzo[d][1,3]oxazine-2,4-dione (684 mg, 3.78 mmol) and heated at 50° C. for 16 h. The mixture was cooled to 0° C. and treated dropwise with 1M aqueous HCl until gas evolution stopped, and stirred for 2 h while allowing to warm to room temperature. The mixture was extracted three times with EtOAc. The combined organic phases were washed sequentially with saturated aqueous NaHCO3 and brine, dried and concentrated. The residue was purified by column chromatography on silica gel (24 g), eluting with EtOAc-hexanes (gradient from 0-30%), to provide 2-amino-N-(3-bromo-2-chlorophenyl)-3-fluorobenzamide as a pale yellow solid (350 mg, 35% yield). Mass spectrum m/z 343, 345 (M+H)+. 1H NMR (400 MHz, chloroform-d) δ 8.46 (dd, J=8.4, 1.3 Hz, 1H), 8.42 (br. s., 1H), 7.43 (dd, J=8.0, 1.4 Hz, 1H), 7.34 (d, J=8.1 Hz, 1H), 7.22 (t, J=8.3 Hz, 1H), 7.15 (ddd, J=11.0, 8.0, 1.2 Hz, 1H), 6.69 (td, J=8.0, 5.1 Hz, 1H), 5.72 (br. s., 2H).

Aufarbeitung

  1. customprepared
  2. temperatureheated at 50° C. for 16 h
  3. temperatureThe mixture was cooled to 0° C.
  4. stirringstirred for 2 h
  5. temperatureto warm to room temperature
  6. extractionThe mixture was extracted three times with EtOAc
  7. washThe combined organic phases were washed sequentially with saturated aqueous NaHCO3 and brine
  8. customdried
  9. concentrationconcentrated
  10. customThe residue was purified by column chromatography on silica gel (24 g)
  11. washeluting with EtOAc-hexanes (gradient from 0-30%)

Quellen und Nachweise

ORD-Eintrag
ord-3802b80f12224e709ce45a0b0b375dbe
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09334290B2

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