5-fluoro-2,3-dihydroisoindol-1-one

反応条件: temp:165.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 500-mL high-pressure bomb reactor was charged with 106b (539 mg, 3.57 mmol), ethanol (30 mL) and excess N,N-ethylmethylamine (50 mL). The mixture was heated at 165° C. for 36 h. After this time, the mixture was concentrated and the resulting residue was purified by flash column chromatography (silica, 98:2 ethyl acetate/triethyl-amine) to afford 106c in 59% yield (397 mg) as a yellow solid: mp 127-129° C.; 1H NMR (500 MHz, DMSO-d6) δ 7.93 (s, 1H), 7.42 (dd, J=7.0, 2.5 Hz, 1H), 6.77-6.75 (m, 2H), 4.23 (s, 2H), 3.46 (q, J=7.0 Hz, 2H), 2.94 (s, 3H), 1.06 (t, J=7.0 Hz, 3H); MS (ESI+) m/z 191.1 (M+H). After this time, the mixture was concentrated the resulting residue was purified by flash column chromatography (silica, 98:2 ethyl acetate/triethyl-amine)

反応条件: temp:165.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 500-mL high-pressure bomb reactor was charged with 106b (539 mg, 3.57 mmol), ethanol (30 mL) and excess N,N-ethylmethylamine (50 mL). The mixture was heated at 165° C. for 36 h. After this time, the mixture was concentrated and the resulting residue was purified by flash column chromatography (silica, 98:2 ethyl acetate/triethyl-amine) to afford 106c in 59% yield (397 mg) as a yellow solid: mp 127-129° C.; 1H NMR (500 MHz, DMSO-d6) δ 7.93 (s, 1H), 7.42 (dd, J=7.0, 2.5 Hz, 1H), 6.77-6.75 (m, 2H), 4.23 (s, 2H), 3.46 (q, J=7.0 Hz, 2H), 2.94 (s, 3H), 1.06 (t, J=7.0 Hz, 3H); MS (ESI+) m/z 191.1 (M+H). After this time, the mixture was concentrated the resulting residue was purified by flash column chromatography (silica, 98:2 ethyl acetate/triethyl-amine)

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

実験手順: A 250-mL Parr reactor bottle was purged with nitrogen and charged with Raney nickel (4.00 g) and a solution of 106a (2.00 g, 11.2 mmol) in ethanol (20 mL). The bottle was attached to a Parr hydrogenator, evacuated, charged with hydrogen gas to a pressure of 50 psi and shaken for 16 h. After this time, the hydrogen was evacuated, and nitrogen was charged into the bottle. Celite 521 (5.00 g) was added, and the mixture was filtered through a pad of Celite 521. The filter cake was washed with ethanol (2×75 mL), and the combined filtrates were concentrated to dryness under reduced pressure to afford a 76% yield of 106b (1.29 g) as a colorless oil: 1H NMR (500 MHz, CDCl3) δ 7.85 (dd, 1H, J=8.5, 5.5 Hz), 7.21-7.16 (m, 2H), 7.05 (br s, 1H), 4.56 (s, 2H). A 250-mL Parr reactor bottle was purged with nitrogen charged with Raney nickel (4.00 g) evacuated charged with hydrogen gas to a pressure of 50 psi After this time, the hydrogen was evacuated nitrogen was charged into the bottle Celite 521 (5.00 g) was added the mixture was filtered through a pad of Celite 521 The filter cake was washed with ethanol (2×75 mL) the combined filtrates were concentrated to dryness under reduced pressure

反応条件: temp:165.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 500-mL high-pressure bomb reactor was charged with 123b (2.20 g, 14.5 mmol) ethanol (30 mL) and excess dimethylamine (50 mL). The mixture was heated at 165° C. for 36h. After this time, the mixture was concentrated and the resulting residue was purified by flash column chromatography (silica, 98:2 ethyl acetate/triethyl-amine) to afford an 81% yield (2.40 g) of 123c as a yellow solid: mp 122-124° C.; 1H NMR (300 MHz, DMSO-d6) δ 7.99 (s, 1H), 7.44 (d, 1H, J=9.3 Hz), 6.77 (m, 2H), 4.24 (s, 2H), 2.99 (s, 6H). After this time, the mixture was concentrated the resulting residue was purified by flash column chromatography (silica, 98:2 ethyl acetate/triethyl-amine)

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

実験手順: A 250-mL Parr reactor bottle was purged with nitrogen and charged with Raney nickel (4.00 g) and a solution of 123a (2.00 g, 11.2 mmol) in ethanol (20 mL). The bottle was attached to a Parr hydrogenator, evacuated, charged with hydrogen gas to a pressure of 50 psi and shaken for 16 h. After this time, the hydrogen was evacuated, and nitrogen was charged into the bottle. Celite 521 (5.00 g) was added, and the mixture was filtered through a pad of Celite 521. The filter cake was washed with ethanol (2×75 mL), and the combined filtrates were concentrated to dryness under reduced pressure to afford a 76% yield of 123b (1.29 g) as a colorless oil: 1H NMR (500 MHz, CDCl3) δ 7.85 (dd, 1H, J=8.5, 5.5 Hz), 7.21-7.16 (m, 2H), 7.05 (br s, 1H), 4.56 (s, 2H). A 250-mL Parr reactor bottle was purged with nitrogen charged with Raney nickel (4.00 g) evacuated charged with hydrogen gas to a pressure of 50 psi After this time, the hydrogen was evacuated nitrogen was charged into the bottle Celite 521 (5.00 g) was added the mixture was filtered through a pad of Celite 521 The filter cake was washed with ethanol (2×75 mL) the combined filtrates were concentrated to dryness under reduced pressure

反応条件: temp:165.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 500-mL high-pressure bomb reactor was charged with 106b (539 mg, 3.57 mmol), ethanol (30 mL) and excess N,N-ethylmethylamine (50 mL). The mixture was heated at 165° C. for 36 h. After this time, the mixture was concentrated and the resulting residue was purified by flash column chromatography (silica, 98:2 ethyl acetate/triethyl-amine) to afford 106c in 59% yield (397 mg) as a yellow solid: mp 127-129° C.; 1H NMR (500 MHz, DMSO-d6) δ 7.93 (s, 1H), 7.42 (dd, J=7.0, 2.5 Hz, 1H), 6.77-6.75 (m, 2H), 4.23 (s, 2H), 3.46 (q, J=7.0 Hz, 2H), 2.94 (s, 3H), 1.06 (t, J=7.0 Hz, 3H); MS (ESI+) m/z 191.1 (M+H). After this time, the mixture was concentrated the resulting residue was purified by flash column chromatography (silica, 98:2 ethyl acetate/triethyl-amine)

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

実験手順: A 250-mL Parr reactor bottle was purged with nitrogen and charged with Raney nickel (4.00 g) and a solution of 106a (2.00 g, 11.2 mmol) in ethanol (20 mL). The bottle was attached to a Parr hydrogenator, evacuated, charged with hydrogen gas to a pressure of 50 psi and shaken for 16 h. After this time, the hydrogen was evacuated, and nitrogen was charged into the bottle. Celite 521 (5.00 g) was added, and the mixture was filtered through a pad of Celite 521. The filter cake was washed with ethanol (2×75 mL), and the combined filtrates were concentrated to dryness under reduced pressure to afford a 76% yield of 106b (1.29 g) as a colorless oil: 1H NMR (500 MHz, CDCl3) δ 7.85 (dd, 1H, J=8.5, 5.5 Hz), 7.21-7.16 (m, 2H), 7.05 (br s, 1H), 4.56 (s, 2H). A 250-mL Parr reactor bottle was purged with nitrogen charged with Raney nickel (4.00 g) evacuated charged with hydrogen gas to a pressure of 50 psi After this time, the hydrogen was evacuated nitrogen was charged into the bottle Celite 521 (5.00 g) was added the mixture was filtered through a pad of Celite 521 The filter cake was washed with ethanol (2×75 mL) the combined filtrates were concentrated to dryness under reduced pressure