6-bromo-2,2-dimethyl-3H-inden-1-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:; See reaction.notes.procedure_details.

実験手順: 6-Bromo-2,2-dimethyl-indan-1-one 45a (7.23 g, 30.3 mmol) was dissolved in 150 mL of trifluoroacetic acid followed by addition of triethylsilane (12.1 mL, 75.6 mmol). The reaction mixture was stirred overnight at room temperature. The reaction was monitored by TLC until the disappearance of the starting materials and then quenched by addition of water. The mixture was concentrated under reduced pressure to remove trifluoroacetic acid. The mixture was adjusted to be basic with saturated aqueous sodium bicarbonate and then extracted with ethyl acetate (50 mL×3). The combined organic extracts were washed with saturated brine, dried over anhydrous sodium sulfate, filtered to remove the drying agent and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound 5-bromo-2,2-dimethyl-indan 45b (14 g) as a colourless oil, which was directly used in the next step. quenched by addition of water The mixture was concentrated under reduced pressure to remove trifluoroacetic acid extracted with ethyl acetate (50 mL×3) The combined organic extracts were washed with saturated brine dried over anhydrous sodium sulfate filtered to remove the drying agent concentrated under reduced pressure The residue was purified by silica gel column chromatography

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

実験手順: A slurry of 6-bromo-2,2-dimethyl-2,3-dihydro-1H-inden-1-one (U.S. Pat. No. 5,401,758) (24.97 g, 0.104 mol) and CuCN (18.7 g, 0.208 mol) in NMP (160 mL) was heated at 175° C. for 4 h. After cooling to rt, the reaction mixture was poured into EtOAc (300 mL) and water (200 mL) with stirring. After 15 min, the solid was collected and the filter cake was rinsed with EtOAc (150 mL). The resulting two layers were separated and the aqueous portion was extracted with EtOAc (150 mL×3). The combined organic layer was washed with brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure to give a dark oil, which was divided into three portions and purified by flash chromatography on silica gel (120 g) eluting with EtOAc/Hexane mixtures to provide the title compound as a near colorless oil after concentration in vacuo (17.8 g, 90% yield). HPLC Ret. time: 2.55 min. LCMS MH+ (m/z) 186.31. 1H NMR: (DMSO-d6, 400 MHz): δ 8.13 (s, 1H), 8.11 (d, 1H), 7.78 (d, 1H), 3.10 (s, 2H), 1.15 (s, 6H). the solid was collected the filter cake was rinsed with EtOAc (150 mL) The resulting two layers were separated the aqueous portion was extracted with EtOAc (150 mL×3) The combined organic layer was washed with brine dried over magnesium sulfate filtered concentrated under reduced pressure to give a dark oil, which purified by flash chromatography on silica gel (120 g) eluting with EtOAc/Hexane

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

実験手順: 6-Bromo-2,2-dimethyl-indan-1-one 45a (7.23 g, 30.3 mmol) was dissolved in 150 mL of trifluoroacetic acid followed by addition of triethylsilane (12.1 mL, 75.6 mmol). The reaction mixture was stirred overnight at room temperature. The reaction was monitored by TLC until the disappearance of the starting materials and then quenched by addition of water. The mixture was concentrated under reduced pressure to remove trifluoroacetic acid. The mixture was adjusted to be basic with saturated aqueous sodium bicarbonate and then extracted with ethyl acetate (50 mL×3). The combined organic extracts were washed with saturated brine, dried over anhydrous sodium sulfate, filtered to remove the drying agent and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound 5-bromo-2,2-dimethyl-indan 45b (14 g) as a colourless oil, which was directly used in the next step. quenched by addition of water The mixture was concentrated under reduced pressure to remove trifluoroacetic acid extracted with ethyl acetate (50 mL×3) The combined organic extracts were washed with saturated brine dried over anhydrous sodium sulfate filtered to remove the drying agent concentrated under reduced pressure The residue was purified by silica gel column chromatography

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

実験手順: 6-Bromo-2,2-dimethyl-indan-1-one 45a (7.23 g, 30.3 mmol) was dissolved in 150 mL of trifluoroacetic acid followed by addition of triethylsilane (12.1 mL, 75.6 mmol). The reaction mixture was stirred overnight at room temperature. The reaction was monitored by TLC until the disappearance of the starting materials and then quenched by addition of water. The mixture was concentrated under reduced pressure to remove trifluoroacetic acid. The mixture was adjusted to be basic with saturated aqueous sodium bicarbonate and then extracted with ethyl acetate (50 mL×3). The combined organic extracts were washed with saturated brine, dried over anhydrous sodium sulfate, filtered to remove the drying agent and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound 5-bromo-2,2-dimethyl-indan 45b (14 g) as a colourless oil, which was directly used in the next step. quenched by addition of water The mixture was concentrated under reduced pressure to remove trifluoroacetic acid extracted with ethyl acetate (50 mL×3) The combined organic extracts were washed with saturated brine dried over anhydrous sodium sulfate filtered to remove the drying agent concentrated under reduced pressure The residue was purified by silica gel column chromatography

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: A slurry of 6-bromo-2,2-dimethyl-2,3-dihydro-1H-inden-1-one (U.S. Pat. No. 5,401,758) (24.97 g, 0.104 mol) and CuCN (18.7 g, 0.208 mol) in NMP (160 mL) was heated at 175° C. for 4 h. After cooling to rt, the reaction mixture was poured into EtOAc (300 mL) and water (200 mL) with stirring. After 15 min, the solid was collected and the filter cake was rinsed with EtOAc (150 mL). The resulting two layers were separated and the aqueous portion was extracted with EtOAc (150 mL×3). The combined organic layer was washed with brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure to give a dark oil, which was divided into three portions and purified by flash chromatography on silica gel (120 g) eluting with EtOAc/Hexane mixtures to provide the title compound as a near colorless oil after concentration in vacuo (17.8 g, 90% yield). HPLC Ret. time: 2.55 min. LCMS MH+ (m/z) 186.31. 1H NMR: (DMSO-d6, 400 MHz): δ 8.13 (s, 1H), 8.11 (d, 1H), 7.78 (d, 1H), 3.10 (s, 2H), 1.15 (s, 6H). the solid was collected the filter cake was rinsed with EtOAc (150 mL) The resulting two layers were separated the aqueous portion was extracted with EtOAc (150 mL×3) The combined organic layer was washed with brine dried over magnesium sulfate filtered concentrated under reduced pressure to give a dark oil, which purified by flash chromatography on silica gel (120 g) eluting with EtOAc/Hexane

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

実験手順: 6-Bromo-2,2-dimethyl-indan-1-one 45a (7.23 g, 30.3 mmol) was dissolved in 150 mL of trifluoroacetic acid followed by addition of triethylsilane (12.1 mL, 75.6 mmol). The reaction mixture was stirred overnight at room temperature. The reaction was monitored by TLC until the disappearance of the starting materials and then quenched by addition of water. The mixture was concentrated under reduced pressure to remove trifluoroacetic acid. The mixture was adjusted to be basic with saturated aqueous sodium bicarbonate and then extracted with ethyl acetate (50 mL×3). The combined organic extracts were washed with saturated brine, dried over anhydrous sodium sulfate, filtered to remove the drying agent and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound 5-bromo-2,2-dimethyl-indan 45b (14 g) as a colourless oil, which was directly used in the next step. quenched by addition of water The mixture was concentrated under reduced pressure to remove trifluoroacetic acid extracted with ethyl acetate (50 mL×3) The combined organic extracts were washed with saturated brine dried over anhydrous sodium sulfate filtered to remove the drying agent concentrated under reduced pressure The residue was purified by silica gel column chromatography