6-fluoro-4H-1,4-benzoxazin-3-one

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 6-Fluoro-4H-benzo[1,4]oxazin-3-one (8173MF55b) (0.090 g, 0.54 mmol), Cs2CO3 (0.263 g, 0.81 mmol) and 3-chloro-1-iodopropane (0.121 g, 0.59 mmol) were mixed according to GP5. CC (SiO2; Heptane/EtOAc 10:1-5) gave the title compound (8173MF55b) (0.102 g, 78%). 1HNMR(CDCl3) δ 6.95-6.91 (m, 1H), 6.82-6.78 (m, 11H), 6.72-6.67 (m, 1H), 4.57 (s, 1H), 4.05 (t, J=7.2 Hz, 2H), 3.62 (t, J=6.2 Hz, 2H), 2.19-2.11 (m, 2H); 13CNMR(CDCl3) δ 164.6, 158.6 (d, J=240.7 Hz), 141.5 (d, J=2.3 Hz), 129.6 (d, J=10.5 Hz), 118.0 (d, J=9.3 Hz), 110.0 (d, J=23.1 Hz), 102.7 (d, J=28.8 Hz), 67.8, 42.3, 39.3, 30.0.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 46 g of ethyl 4-fluoro-2-nitrophenoxyacetate, prepared in Example 18, in 500 ml of methanol is hydrogenated under atmospheric pressure in the presence of Raney nickel. After absorption of the theoretical quantity of hydrogen, the catalyst is filtered off, the solution is concentrated in vacuo and the residue is taken up in either, from which it crystallizes. The crystals formed are filtered off, washed with ether and dried. 28 g of 6-fluoro-2H-1,4-benzoxazin-3(4H)-one are thus obtained in the form of crystals of melting point 206°-207° C. After absorption of the theoretical quantity of hydrogen the catalyst is filtered off the solution is concentrated in vacuo crystallizes The crystals formed are filtered off washed with ether dried

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: LiAlH4 (14.7 mmol, 1 M solution in THF) is added to a solution of 6-fluoro-4H-benzo[1,4]oxazin-3-one (1.23 g, 7.35 mmol) in THF at rt and heated to reflux for 2 hrs. The reaction mixture is quenched with a few drops of water followed by slow addition of ethyl acetate (10 mL). The solid is filtered off, and washed with EtOAc. The filtrate is concentrated in vacuo to afford 6-fluoro-3,4-dihydro-2H-benzo[1,4]oxazine (1 g). MS: 154 (M+H). heated to reflux for 2 hrs The reaction mixture is quenched with a few drops of water followed by slow addition of ethyl acetate (10 mL) The solid is filtered off washed with EtOAc The filtrate is concentrated in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: LiAlH4 (14.7 mmol, 1 M solution in THF) is added to a solution of 6-fluoro-4H-benzo[1,4]oxazin-3-one (1.23 g, 7.35 mmol) in THF at rt and heated to reflux for 2 hrs. The reaction mixture is quenched with a few drops of water followed by slow addition of ethyl acetate (10 mL). The solid is filtered off, and washed with EtOAc. The filtrate is concentrated in vacuo to afford 6-fluoro-3,4-dihydro-2H-benzo[1,4]oxazine (1 g). MS: 154 (M+H). heated to reflux for 2 hrs The reaction mixture is quenched with a few drops of water followed by slow addition of ethyl acetate (10 mL) The solid is filtered off washed with EtOAc The filtrate is concentrated in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 6-Fluoro-4H-benzo[1,4]oxazin-3-one (95MF88) (2.54 g, 15.2 mmol), (R)-3-bromo-2-methylpropoxy-tert-butyldimethylsilane (4.07 g, 15.2 mmol) and Cs2CO3 (12.38 g, 38 mmol) were mixed according to GP7. CC (SiO2; Heptane/EtOAc 9:1) gave the title compound (111MF01) (4.09 g, 76%). 1H NMR (CDCl3) δ 6.93-6.87 (m, 1H), 6.92-6.88 (m, 1H), 6.68-6.63 (m, 1H), 4.56 (m, 2H), 4.01 (m, 1H), 3.78 (m, 1H), 3.58 (m, 1H), 3.45 (m, 1H), 2.11 (m, 1H), 0.92 (s, 12H), 0.06 (d, J=0.8 Hz, 6H); 13C NMR (CDCl3) δ 164.8, 158.5 (d, J=239.9 Hz), 141.6 (d, J=2.7 Hz), 130.1 (d, J=10.7 Hz), 117.6 (d, J=9.3 Hz), 109.6 (d, J=23.1 Hz), 103.6 (d, J=28.8 Hz), 67.8, 65.9, 44.2, 34.5, 26.0, 18.4, 14.9, −5.4, −5.4.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 6-Fluoro-4H-benzo[1,4]oxazin-3-one (8173MF55b) (0.090 g, 0.54 mmol), Cs2CO3 (0.263 g, 0.81 mmol) and 3-chloro-1-iodopropane (0.121 g, 0.59 mmol) were mixed according to GP5. CC (SiO2; Heptane/EtOAc 10:1-5) gave the title compound (8173MF55b) (0.102 g, 78%). 1HNMR(CDCl3) δ 6.95-6.91 (m, 1H), 6.82-6.78 (m, 1H), 6.72-6.67 (m, 1H), 4.57 (s, 1H), 4.05 (t, J=7.2 Hz, 2H), 3.62 (t, J=6.2 Hz, 2H), 2.19-2.11 (m, 2H); 13CNMR(CDCl3) δ 164.6, 158.6 (d, J=240.7 Hz), 141.5 (d, J=2.3 Hz), 129.6 (d, J=10.5 Hz), 118.0 (d, J=9.3 Hz), 110.0 (d, J=23.1 Hz), 102.7 (d, J=28.8 Hz), 67.8, 42.3, 39.3, 30.0.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 6-Fluoro-4H-benzo[1,4]oxazin-3-one (95MF88) (2.54 g, 15.2 mmol), (R)-3-bromo-2-methylpropoxy-tert-butyldimethylsilane (4.07 g, 15.2 mmol) and Cs2CO3 (12.38 g, 38 mmol) were mixed according to GP7. CC (SiO2; Heptane/EtOAc 9:1) gave the title compound (111MF01) (4.09 g, 76%). 1H NMR (CDCl3) δ 6.93-6.87 (m, 1H), 6.92-6.88 (m, 1H), 6.68-6.63 (m, 1H), 4.56 (m, 2H), 4.01 (m, 1H), 3.78 (m, 1H), 3.58 (m, 1H), 3.45 (m, 1H), 2.11 (m, 1H), 0.92 (s, 12H), 0.06 (d, J=0.8 Hz, 6H); 13C NMR (CDCl3) δ 164.8, 158.5 (d, J=239.9 Hz), 141.6 (d, J=2.7 Hz), 130.1 (d, J=10.7 Hz), 117.6 (d, J=9.3 Hz), 109.6 (d, J=23.1 Hz), 103.6 (d, J=28.8 Hz), 67.8, 65.9, 44.2, 34.5, 26.0, 18.4, 14.9, −5.4, −5.4.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 6-Fluoro-4H-benzo[1,4]oxazin-3-one (8173MF55b) (0.090 g, 0.54 mmol), Cs2CO3 (0.263 g, 0.81 mmol) and 3-chloro-1-iodopropane (0.121 g, 0.59 mmol) were mixed according to GP5. CC (SiO2; Heptane/EtOAc 10:1-5) gave the title compound (8173MF55b) (0.102 g, 78%). 1HNMR(CDCl3) δ 6.95-6.91 (m, 1H), 6.82-6.78 (m, 1H), 6.72-6.67 (m, 1H), 4.57 (s, 1H), 4.05 (t, J=7.2 Hz, 2H), 3.62 (t, J=6.2 Hz, 2H), 2.19-2.11 (m, 2H); 13CNMR(CDCl3) δ 164.6, 158.6 (d, J=240.7 Hz), 141.5 (d, J=2.3 Hz), 129.6 (d, J=10.5 Hz), 118.0 (d, J=9.3 Hz), 110.0 (d, J=23.1 Hz), 102.7 (d, J=28.8 Hz), 67.8, 42.3, 39.3, 30.0.