Ethyl chloroformate → 3-(4-Bromo-2-fluoro-benzyl)-7-methoxy benzo[e][1,3]oxazine-2,4-dione

HRID 2229531

Reaktionsgleichung

Reaktionsgleichung von HRID 2229531
[OH:1][C:2]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.C(N(C(C)C)CC)(C)C.Cl[C:23](OCC)=[O:24].[F:28][C:29]1[CH:36]=[C:35]([Br:37])[CH:34]=[CH:33][C:30]=1[CH2:31][NH2:32]>O1CCCC1.C(OCC)(=O)C>[Br:37][C:35]1[CH:34]=[CH:33][C:30]([CH2:31][N:32]2[C:4](=[O:6])[C:3]3[CH:7]=[CH:8][C:9]([O:11][CH3:12])=[CH:10][C:2]=3[O:1][C:23]2=[O:24])=[C:29]([F:28])[CH:36]=1

Komponenten

7

Edukt 4

HCID 10928Ethyl chloroformateHCID 752314-Methoxysalicylic AcidHCID 81531Diisopropylethylamine2×HCID 3770848(4-Bromo-2-fluorophenyl)methanamine

Produkt 1

HCID 184681743-(4-Bromo-2-fluoro-benzyl)-7-methoxy benzo[e][1,3]oxazine-2,4-dioneAusbeute 36,5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittel2×HCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

A solution of 2-hydroxy-4-methoxybenzoic acid (2.04 g, 12.2 mmol) in tetrahydrofuran (20 mL, 0.6 M) was cooled to 0° C. After being treated with diisopropylethylamine (4.4 mL, 25.3 mmol) and ethyl chloroformate (2.4 mL, 25.1 mmol), the mixture was stirred at room temperature for 1 h and subsequently treater with a solution of 2-fluoro-4-bromobenzylamine (2.92 g, 12.1 mmol) and diisopropylethylamine (4.4 mL, 25.3 mmol) in tetrahydrofuran (15 mL). After stirring at room temperature for 22 h, the reaction mixture was diluted ethyl acetate and successively washed with 2 N HCl, saturated aq NaHCO3 and saturated aq NaCl. The organic layer was dried over Na2SO4, filtered and concentrated. The crude solid was purified by recrystallization with heptane and ethyl acetate to give 3-(4-bromo-2-fluoro-benzyl)-7-methoxy benzo[e][1,3]oxazine-2,4-dione (1.68 g, 36%): 1H NMR (DMSO-d6, 300 MHz) δ 7.87 (d, J=8.4 Hz, 1H), 7.53 (dd, J1=10.5 Hz, J2=1.1 Hz, 1H), 7.33-7.34 (m, 2H), 7.03-6.99 (m, 2H), 5.02 (s, 2H), 3.87 (s, 3H).

Aufarbeitung

  1. stirringAfter stirring at room temperature for 22 h
  2. washsuccessively washed with 2 N HCl, saturated aq NaHCO3 and saturated aq NaCl
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude solid was purified by recrystallization with heptane and ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-c748ca75ee814d998d41de1ec7b310a6
Quelldatensatz
uspto-grants-2002_07
Patentnummer
US06420426B1

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