Reaktion #545124

Reaktionsgleichung

diisopropylethylamine

ethyl chloroformate

2-hydroxy-4-methoxybenzoic acid

2-fluoro-4-bromobenzylamine

diisopropylethylamine

→

3-(4-bromo-2-fluoro-benzyl)-7-methoxy benzo[e][1,31 oxazine-2,4-dione

Ausbeute 36.5%

Lösungsmittel

ethyl acetate

tetrahydrofuran

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGAfter stirring at room temperature for 22 h
2. 2
   Waschensuccessively washed with 2 N HCl, saturated aq NaHCO3 and saturated aq NaCl
3. 3
   TrocknenThe organic layer was dried over Na2SO4
4. 4
   Filtrationfiltered
5. 5
   Einengenconcentrated
6. 6
   SonstigeThe crude solid was purified by recrystallization with heptane and ethyl acetate

Vorschrift

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 treated 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][1,31 oxazine-2,4-dione (1.68 g, 36%): 1H NMR (DMSO-d6, 300 MHz) δ 7.87 (d, J=8.4 Hz, 1 H), 7.53 (dd, J1=10.5 Hz, J2=1.1 Hz, 1 H), 7.33–7.34 (m, 2 H), 7.03–6.99 (m, 2 H), 5.02 (s, 2 H), 3.87 (s, 3 H).

Quelle