6,7-difluoro-4H-1,4-benzoxazin-3-one

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A reaction flask was charged with 6,7-difluoro-4H-benzo[1.4]oxazin-3-one (1.5 g, 8.1 mmol), 1-chloro-3-iodopropane (1.44 g, 8.1 mmol), and Cs2CO3 (4.0 g, 12.2 mmol) in MeCN (10 mL) and stirred at rt for 40 h. The reaction mixture was concentrated, water added, and the product extracted into EtOAc. The combined organic phases were dried over Na2SO4, filtered, and concentrated. The product was purified by flash column chromatography (SiO2; n-heptane/EtOAc 2:1) to give the title compound (1.88 g, 89%). 1H NMR (CDCl3) d 6.99 (dd, J=8.0 Hz, J=5.6 Hz, 1H), 6.79-6.72 (m, 2H), 4.59 (s, 2H), 4.08 (t, J=7.2 Hz, 2H), 3.62 (t, J=6.0 Hz, 2H) 2.18-2.10 (m, 2H); 13C NMR (CDCl3) d 163.9, 159.1 (d, J=244.1 Hz), 146.4 (d, J=11.9 Hz), 124.9 (d, J=3.0 Hz), 115.4 (d, J=9.6 Hz), 109.5 (d, J=22.7 Hz), 105.4 (d, J=26.2 Hz), 67.7, 42.4, 39.2, 30.1. The reaction mixture was concentrated water added the product extracted into EtOAc The combined organic phases were dried over Na2SO4 filtered concentrated The product was purified by flash column chromatography (SiO2; n-heptane/EtOAc 2:1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A crude of 2-amino-4,5-diflourophenol (2.67 g, 18.4 mmol), 2-chloroacetyl chloride (2.28 g, 20 mmol) and K2CO3 (5.34 g, 38.6 mmol) were mixed according to GP1. Purified by column chromatography (SiO2; heptanes/EtOAc 4:1 to 1:1) to give the title compound (2.17 g, 64%). Rf=0.43 (heptanes/EtOAc 1:1); Mp=214.5-219.2° C.; 1H NMR (CD3OD) d 6.90 (dd, J=11.4 Hz, J=7.2 Hz, 1H), 6.80 (dd, J=11.0 Hz, J=7.7 Hz, 1H), 4.56 (s, 2H); 13C NMR (CD3OD) d 167.0, 147.0 (dd, J=243.5 Hz, J=13.8 Hz), 146.9 (dd, J=240.0 Hz, J=13.8 Hz), 141.2 (dd, J=9.8 Hz, J=3.0 Hz), 124.8 (dd, J=8.7 Hz, J=3.0 Hz), 106.9 (dd, J=22.0 Hz, J=6.9 Hz), 105.5 (dd, J=23.1 Hz, J=4.6 Hz), 68.1 (t, J=6.5 Hz). Purified by column chromatography (SiO2; heptanes/EtOAc 4:1 to 1:1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A reaction flask was charged with 6,7-difluoro-4H-benzo[1,4]oxazin-3-one (1.5 g, 8.1 mmol), 1-chloro-3-iodopropane (1.44 g, 8.1 mmol), and Cs2CO3 (4.0 g, 12.2 mmol) in MeCN (10 mL) and stirred at rt for 40 h. The reaction mixture was concentrated, water added, and the product extracted into EtOAc. The combined organic phases were dried over Na2SO4, filtered, and concentrated. The product was purified by flash column chromatography (SiO2; n-heptane/EtOAc 2:1) to give the title compound (1.88 g, 89%). 1H NMR (CDCl3) δ 6.99 (dd, J=8.0 Hz, J=5.6 Hz, 1H), 6.79-6.72 (m, 2H), 4.59 (s, 2H), 4.08 (t, J=7.2 Hz, 2H), 3.62 (t, J=6.0 Hz, 2H) 2.18-2.10 (m, 2H); 13C NMR (CDCl3) δ 163.9, 159.1 (d, J=244.1 Hz), 146.4 (d, J=11.9 Hz), 124.9 (d, J=3.0 Hz), 115.4 (d, J=9.6 Hz), 109.5 (d, J=22.7 Hz), 105.4 (d, J=26.2 Hz), 67.7, 42.4, 39.2, 30.1. The reaction mixture was concentrated water added the product extracted into EtOAc The combined organic phases were dried over Na2SO4 filtered concentrated The product was purified by flash column chromatography (SiO2; n-heptane/EtOAc 2:1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A crude of 2-amino-4,5-difluorophenol (2.67 g, 18.4 mmol), 2-chloroacetyl chloride (2.28 g, 20 mmol) and K2CO3 (5.34 g, 38.6 mmol) were mixed according to GP1. Purified by column chromatography (SiO2; heptanes/EtOAc 4:1 to 1:1) to give the title compound (2.17 g, 64%). Rf=0.43 (heptanes/EtOAc 1:1); Mp=214.5-219.2° C.; 1H NMR (CD3OD) δ 6.90 (dd, J=11.4 Hz, J=7.2 Hz, 1H), 6.80 (dd, J=11.0 Hz, J=7.7 Hz, 1H), 4.56 (s, 2H); 13C NMR (CD3OD) δ 167.0, 147.0 (dd, J=243.5 Hz, J=13.8 Hz), 146.9 (dd, J=240.0 Hz, J=13.8 Hz), 141.2 (dd, J=9.8 Hz, J=3.0 Hz), 124.8 (dd, J=8.7 Hz, J=3.0 Hz), 106.9 (dd, J=22.0 Hz, J=6.9 Hz), 105.5 (dd, J=23.1 Hz, J=4.6 Hz), 68.1 (t, J=6.5 Hz). Purified by column chromatography (SiO2; heptanes/EtOAc 4:1 to 1:1)