6-fluoro-1,2,3,9-tetrahydrocarbazol-4-one

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: 6-Fluoro-1,2,3,9-tetrahydro-4H-carbazol-4-one (0.3940 g, 0.0019 mol) is added to a slurry of pentane-washed NaH (0.0966 g, 0.0024 mol) in DMF (3 mL) and after stirring for 10 min, p-fluorobenzyl bromide (0.29 mL, 0.0023 mol) is added. After stirring for 4 h at room temperature, the mixture is partitioned between water and ethyl acetate. The combined organic layers are dried over sodium sulfate and concentrated to dryness. The resulting solids are chromatographed on silica gel (100 mL) using methanol/dichloromethane (0.5/99.5) to give 0.5678 g (94%) of the title compound. An aliquot is recrystallized from ethyl acetate/heptane; mp 182.5-183° C.; MS (ESI+) for C19H15F2NO m/z 312.2 (M+H)+; IR (drift) 1631, 1511, 1483, 1466, 1449, 1256, 1228, 1218, 1137, 1094, 867, 836, 813, 808, 802 cm−1; 1H NMR (CDCl3) δ2.24, 2.58, 2.86, 5.28, 6.94, 7.13, 7.96. Anal. Calcd for C19H15F2NO: C, 73.30; H, 4.86; N, 4.50. Found: C, 73.27; H, 4.92; N, 4.54. After stirring for 4 h at room temperature the mixture is partitioned between water and ethyl acetate The combined organic layers are dried over sodium sulfate concentrated to dryness The resulting solids are chromatographed on silica gel (100 mL)

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

Procedure: 6-Fluoro-1,2,3,9-tetrahydro-4H-carbazol-4-one (0.3940 g, 0.0019 mol) is added to a slurry of pentane-washed NaH (0.0966 g, 0.0024 mol) in DMF (3 mL) and after stirring for 10 min, p-fluorobenzyl bromide (0.29 mL, 0.0023 mol) is added. After stirring for 4 h at room temperature, the mixture is partitioned between water and ethyl acetate. The combined organic layers are dried over sodium sulfate and concentrated to dryness. The resulting solids are chromatographed on silica gel (100 mL) using methanol/dichloromethane (0.5/99.5) to give 0.5678 g (94%) of the title compound. An aliquot is recrystallized from ethyl acetate/heptane; mp 182.5-183° C.; MS (ESI+) for C19H15F2NO m/z 312.2 (M+H)+; IR (drift) 1631, 1511, 1483, 1466, 1449, 1256, 1228, 1218, 1137, 1094, 867, 836, 813, 808, 802 cm−1; 1H NMR (CDCl3) δ2.24, 2.58, 2.86, 5.28, 6.94, 7.13, 7.96. Anal. Calcd for C19H15F2NO: C, 73.30; H, 4.86; N, 4.50. Found: C, 73.27; H, 4.92; N, 4.54. After stirring for 4 h at room temperature the mixture is partitioned between water and ethyl acetate The combined organic layers are dried over sodium sulfate concentrated to dryness The resulting solids are chromatographed on silica gel (100 mL)

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

Procedure: 6-Fluoro-1,2,3,9-tetrahydro-4H-carbazol-4-one (0.3938 g, 0.0019 mol) is added to a slurry of pentane-washed NaH (0.0970 g, 0.0024 mol) in DMF (3 mL) and after stirring for 10 min, benzyl bromide (0.28 mL, 0.0024 mol) is added. After stirring for 4 h at room temperature, the mixture is partitioned between water and ethyl acetate. The combined organic layers are dried over sodium sulfate and concentrated to dryness. The resulting solids are chromatographed on silica gel (200 mL) using dichloromethane/heptane (60/40 to 80/20 to 100/0) to give 0.3681 g (65%) of the title compound. An aliquot is recrystallized from ethyl acetate/heptane; MS (ESI+) for C19H16FNO m/z 294.2 (M+H)+; IR (drift) 1634, 1523, 1483, 1466, 1447, 1357, 1254, 1138, 900, 868, 803, 799, 759, 729, 700 cm−1; 1H NMR (CDCl3) δ2.22, 2.59, 2.88, 5.32, 6.95, 7.01, 7.15, 7.30, 7.96. Anal. Calcd for C19H16FNO: C, 77.80; H, 5.50; N, 4.78. Found: C, 77.65; H, 5.39; N, 4.69. After stirring for 4 h at room temperature the mixture is partitioned between water and ethyl acetate The combined organic layers are dried over sodium sulfate concentrated to dryness The resulting solids are chromatographed on silica gel (200 mL)

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

Procedure: 6-Fluoro-1,2,3,9-tetrahydro-4H-carbazol-4-one (0.3938 g, 0.0019 mol) is added to a slurry of pentane-washed NaH (0.0970 g, 0.0024 mol) in DMF (3 mL) and after stirring for 10 min, benzyl bromide (0.28 mL, 0.0024 mol) is added. After stirring for 4 h at room temperature, the mixture is partitioned between water and ethyl acetate. The combined organic layers are dried over sodium sulfate and concentrated to dryness. The resulting solids are chromatographed on silica gel (200 mL) using dichloromethane/heptane (60/40 to 80/20 to 100/0) to give 0.3681 g (65%) of the title compound. An aliquot is recrystallized from ethyl acetate/heptane; MS (ESI+) for C19H16FNO m/z 294.2 (M+H)+; IR (drift) 1634, 1523, 1483, 1466, 1447, 1357, 1254, 1138, 900, 868, 803, 799, 759, 729, 700 cm−1; 1H NMR (CDCl3) δ2.22, 2.59, 2.88, 5.32, 6.95, 7.01, 7.15, 7.30, 7.96. Anal. Calcd for C19H16FNO: C, 77.80; H, 5.50; N, 4.78. Found: C, 77.65; H, 5.39; N, 4.69. After stirring for 4 h at room temperature the mixture is partitioned between water and ethyl acetate The combined organic layers are dried over sodium sulfate concentrated to dryness The resulting solids are chromatographed on silica gel (200 mL)

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

Procedure: The product of Stage (ii) (7.28 g), potassium carbonate (9.90 g), acetone (70 ml), and dimethylsulphate (5.1 ml) were vigorously stirred at room temperature overnight under nitrogen. The mixture was concentrated to one half of its volume and then stirred with water (350 ml) for 30 min. The mixture was filtered off, washed with water (50 ml), air-dried for 1 h, and dried in vacuo over phosphorus pentoxide to give the title compound as needles (7.59 g), m.p. 157.5°-158.5°. The mixture was concentrated to one half of its volume The mixture was filtered off washed with water (50 ml) air-dried for 1 h dried in vacuo over phosphorus pentoxide

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: The product of Stage (ii) (7.28 g), potassium carbonate (9.90 g), acetone (70 ml), and dimethylsulphate (5.1 ml) were vigorously stirred at room temperature overnight under nitrogen. The mixture was concentrated to one half of its volume and then stirred with water (350 ml) for 30 min. The mixture was filtered off, washed with water (50 ml), air-dried for 1 h, and dried in vacuo over phosphorus pentoxide to give the title compound as needles (7.59 g), m.p. 157.5°-158.5°. The mixture was concentrated to one half of its volume The mixture was filtered off washed with water (50 ml) air-dried for 1 h dried in vacuo over phosphorus pentoxide

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

Procedure: 6-Fluoro-1,2,3,9-tetrahydro-4H-carbazol-4-one (0.3940 g, 0.0019 mol) is added to a slurry of pentane-washed NaH (0.0966 g, 0.0024 mol) in DMF (3 mL) and after stirring for 10 min, p-fluorobenzyl bromide (0.29 mL, 0.0023 mol) is added. After stirring for 4 h at room temperature, the mixture is partitioned between water and ethyl acetate. The combined organic layers are dried over sodium sulfate and concentrated to dryness. The resulting solids are chromatographed on silica gel (100 mL) using methanol/dichloromethane (0.5/99.5) to give 0.5678 g (94%) of the title compound. An aliquot is recrystallized from ethyl acetate/heptane; mp 182.5-183° C.; MS (ESI+) for C19H15F2NO m/z 312.2 (M+H)+; IR (drift) 1631, 1511, 1483, 1466, 1449, 1256, 1228, 1218, 1137, 1094, 867, 836, 813, 808, 802 cm−1; 1H NMR (CDCl3) δ2.24, 2.58, 2.86, 5.28, 6.94, 7.13, 7.96. Anal. Calcd for C19H15F2NO: C, 73.30; H, 4.86; N, 4.50. Found: C, 73.27; H, 4.92; N, 4.54. After stirring for 4 h at room temperature the mixture is partitioned between water and ethyl acetate The combined organic layers are dried over sodium sulfate concentrated to dryness The resulting solids are chromatographed on silica gel (100 mL)

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

Procedure: 6-Fluoro-1,2,3,9-tetrahydro-4H-carbazol-4-one (0.3938 g, 0.0019 mol) is added to a slurry of pentane-washed NaH (0.0970 g, 0.0024 mol) in DMF (3 mL) and after stirring for 10 min, benzyl bromide (0.28 mL, 0.0024 mol) is added. After stirring for 4 h at room temperature, the mixture is partitioned between water and ethyl acetate. The combined organic layers are dried over sodium sulfate and concentrated to dryness. The resulting solids are chromatographed on silica gel (200 mL) using dichloromethane/heptane (60/40 to 80/20 to 100/0) to give 0.3681 g (65%) of the title compound. An aliquot is recrystallized from ethyl acetate/heptane; MS (ESI+) for C19H16FNO m/z 294.2 (M+H)+; IR (drift) 1634, 1523, 1483, 1466, 1447, 1357, 1254, 1138, 900, 868, 803, 799, 759, 729, 700 cm−1; 1H NMR (CDCl3) δ2.22, 2.59, 2.88, 5.32, 6.95, 7.01, 7.15, 7.30, 7.96. Anal. Calcd for C19H16FNO: C, 77.80; H, 5.50; N, 4.78. Found: C, 77.65; H, 5.39; N, 4.69. After stirring for 4 h at room temperature the mixture is partitioned between water and ethyl acetate The combined organic layers are dried over sodium sulfate concentrated to dryness The resulting solids are chromatographed on silica gel (200 mL)

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

Procedure: The product of Stage (ii) (7.28 g), potassium carbonate (9.90 g), acetone (70 ml), and dimethylsulphate (5.1 ml) were vigorously stirred at room temperature overnight under nitrogen. The mixture was concentrated to one half of its volume and then stirred with water (350 ml) for 30 min. The mixture was filtered off, washed with water (50 ml), air-dried for 1 h, and dried in vacuo over phosphorus pentoxide to give the title compound as needles (7.59 g), m.p. 157.5°-158.5°. The mixture was concentrated to one half of its volume The mixture was filtered off washed with water (50 ml) air-dried for 1 h dried in vacuo over phosphorus pentoxide