bicyclo[3.3.1]nonan-9-one

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

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Add successively 21 mL of water, 1.12 g (22.8 mmol) of sodium cyanide, 4.52 mL (54.27 mmol) of 12N aqueous ammonia solution and 2.32 g (43.41 mmol) of NH4Cl to a solution of 3 g (21.7 mmol) of bicyclo[3.3.1]nonan-9-one in 40 mL of EtOH. Stir the reaction mixture for 18 h at 50° C. Then add 5 mL of 12N aqueous ammonia solution and heat the mixture again for 4 h at 50° C. Cool the solution to RT then distribute in 100 mL of a 1:1 mixture of ether/1N aqueous soda solution. After extraction, wash the organic phase with 3×50 mL of water, dry over Na2SO4 and concentrate under reduced pressure. Take up the residue obtained in 50 mL of ether and then treat for 1 minute with a gentle stream of hydrogen chloride. Filter the hydrochloride thus obtained, wash with 20 mL of ether and distribute in 100 mL of a 1:1 mixture of DCM/saturated aqueous solution of Na2CO3. Extract the aqueous phase again with 50 mL of DCM, then combine the organic phases, wash with 2×20 mL of water and dry over Na2SO4. After concentration under reduced pressure, we obtain 1.88 g of 9-aminobicyclo[3.3.1]nonane-9-carbonitrile in the form of oil. heat the mixture again for 4 h at 50° C Cool the solution to RT After extraction wash the organic phase with 3×50 mL of water dry over Na2SO4 concentrate under reduced pressure obtained in 50 mL of ether Filter the hydrochloride thus obtained wash with 20 mL of ether distribute in 100 mL of a 1:1 mixture of DCM/saturated aqueous solution of Na2CO3 Extract the aqueous phase again with 50 mL of DCM wash with 2×20 mL of water dry over Na2SO4 After concentration under reduced pressure, we

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Add successively 21 mL of water, 1.12 g (22.8 mmol) of sodium cyanide, 4.52 mL (54.27 mmol) of 12N aqueous ammonia solution and 2.32 g (43.41 mmol) of NH4Cl to a solution of 3 g (21.7 mmol) of bicyclo[3.3.1]nonan-9-one in 40 mL of EtOH. Stir the reaction mixture for 18 h at 50° C. Then add 5 mL of 12N aqueous ammonia solution and heat the mixture again for 4 h at 50° C. Cool the solution to RT then distribute in 100 mL of a 1:1 mixture of ether/1N aqueous soda solution. After extraction, wash the organic phase with 3×50 mL of water, dry over Na2SO4 and concentrate under reduced pressure. Take up the residue obtained in 50 mL of ether and then treat for 1 minute with a gentle stream of hydrogen chloride. Filter the hydrochloride thus obtained, wash with 20 mL of ether and distribute in 100 mL of a 1:1 mixture of DCM/saturated aqueous solution of Na2CO3. Extract the aqueous phase again with 50 mL of DCM, then combine the organic phases, wash with 2×20 mL of water and dry over Na2SO4. After concentration under reduced pressure, we obtain 1.88 g of 9-aminobicyclo[3.3.1]nonane-9-carbonitrile in the form of oil. heat the mixture again for 4 h at 50° C Cool the solution to RT After extraction wash the organic phase with 3×50 mL of water dry over Na2SO4 concentrate under reduced pressure obtained in 50 mL of ether Filter the hydrochloride thus obtained wash with 20 mL of ether distribute in 100 mL of a 1:1 mixture of DCM/saturated aqueous solution of Na2CO3 Extract the aqueous phase again with 50 mL of DCM wash with 2×20 mL of water dry over Na2SO4 After concentration under reduced pressure, we

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

Procedure: A solution was prepared by dissolving 10 g (0.054 mole) of 1-acetyl-2-naphthol, 8.29 g (0.06 mole) of bicyclo[3,3,1]nonan-9-one and 8.7 g (0.10 mole) of morpholine in 300 cc of toluene, and the solution was boiled for 5 hours and water was separated. After termination of the reaction, toluene was removed under reduced pressure and the remaining chromanone compound was recrystallized from acetone. Then, the chromanone compound was dissolved in 200 cc of methanol and lithium aluminum hydride was added to the solution to form a chromanol compound. Then, 6.49 g of this chromanol compound was heated at 170° C. to 180° C. together with anhydrous copper sulfate in a carbon dioxide current for 10 minutes, and the obtained brown viscous liquid was purified by the chromatography on silica gel to obtain 5.8 g of a chromene compound represented by the following formula: ##STR162## A solution was prepared water was separated After termination of the reaction, toluene was removed under reduced pressure the remaining chromanone compound was recrystallized from acetone Then, the chromanone compound was dissolved in 200 cc of methanol lithium aluminum hydride was added to the solution

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

Procedure: A solution was prepared by dissolving 10 g (0.054 mole) of 1-acetyl-2-naphthol, 8.29 g (0.06 mole) of bicyclo[3,3,1]nonan-9-one and 8.7 g (0.10 mole) of morpholine in 300 cc of toluene, and the solution was boiled for 5 hours and water was separated. After termination of the reaction, toluene was removed under reduced pressure and the remaining chromanone compound was recrystallized from acetone. Then, the chromanone compound was dissolved in 200 cc of methanol and lithium aluminum hydride was added to the solution to form a chromanol compound. Then, 6.49 g of this chromanol compound was heated at 170° C. to 180° C. together with anhydrous copper sulfate in a carbon dioxide current for 10 minutes, and the obtained brown viscous liquid was purified by the chromatography on silica gel to obtain 5.8 g of a chromene compound represented by the following formula: ##STR162## A solution was prepared water was separated After termination of the reaction, toluene was removed under reduced pressure the remaining chromanone compound was recrystallized from acetone Then, the chromanone compound was dissolved in 200 cc of methanol lithium aluminum hydride was added to the solution

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

Procedure: A solution was prepared by dissolving 10 g (0.054 mole) of 1-hydroxy-2-acetonaphthone, 8.29 g (0.06 mole) of bicyclo[3,3,1]nonan-9-one and 8 g (0.113 mole) of pyrrolidine in 300 cc of toluene, and the solution was boiled for 10 hours and water was separated. After termination of the reaction, toluene was removed under reduced pressure, and the remaining chromanone compound was crystallized with acetone. Then, the chromanone compound was dissolved in 200 cc of methanol and sodium boron hydride was gradually added to the solution to form a chromanol compound. Then, 7.47 g of this chromanol compound was heated at 150° C. to 160° C. together with 4.5 g of anhydrous copper sulfate in a carbon dioxide current for 10 minutes, and the obtained brown viscous liquid was purified by the chromatography on silica gel to obtain 6.9 g of a chromene compound represented by the following formula: ##STR161## A solution was prepared water was separated After termination of the reaction, toluene was removed under reduced pressure the remaining chromanone compound was crystallized with acetone Then, the chromanone compound was dissolved in 200 cc of methanol sodium boron hydride was gradually added to the solution

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

Procedure: A solution was prepared by dissolving 10 g (0.054 mole) of 1-hydroxy-2-acetonaphthone, 8.29 g (0.06 mole) of bicyclo[3,3,1]nonan-9-one and 8 g (0.113 mole) of pyrrolidine in 300 cc of toluene, and the solution was boiled for 10 hours and water was separated. After termination of the reaction, toluene was removed under reduced pressure, and the remaining chromanone compound was crystallized with acetone. Then, the chromanone compound was dissolved in 200 cc of methanol and sodium boron hydride was gradually added to the solution to form a chromanol compound. Then, 7.47 g of this chromanol compound was heated at 150° C. to 160° C. together with 4.5 g of anhydrous copper sulfate in a carbon dioxide current for 10 minutes, and the obtained brown viscous liquid was purified by the chromatography on silica gel to obtain 6.9 g of a chromene compound represented by the following formula: ##STR161## A solution was prepared water was separated After termination of the reaction, toluene was removed under reduced pressure the remaining chromanone compound was crystallized with acetone Then, the chromanone compound was dissolved in 200 cc of methanol sodium boron hydride was gradually added to the solution

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

Procedure: In a 3-neck round-bottomed flask equipped with a reflux condenser and a nitrogen inlet, TiCl4 (0.51 mL, 4.67 mmol) was slowly added to a suspension of zinc powder (0.63 g, 9.60 mmol) in dry THF (13 mL) at room temperature. The reaction mixture was heated at reflux for 2.5 h. The reaction mixture was taken out of the oil bath and a solution of (4-bromophenyl)(4-hydroxyphenyl)methanone (2) (0.35 g, 1.26 mmol) and bicyclo[3.3.1]nonan-9-one (0.52 g, 3.79 mmol) in dry THF (13 mL) was added. The reaction mixture was heated at reflux for 2 h. The reaction mixture was allowed to cool at RT. Water (10 mL) was added to the reaction mixture via a syringe followed by 10% K2CO3 (10 mL). The reaction mixture was filtered through a pad of Celite. The pad of Celite was washed with EtOAc. The filtrate was transferred to a separatory funnel and the layers were separated. The organic layer was washed with brine, dried (MgSO4), filtered, and the filtrate was concentrated to give an oily residue. The crude product was adsorbed onto silica and purified by flash column chromatography using SiO2 and a hexanes:EtOAc gradient (100:0 to 75:25) to afford compound 43 as a white powder (0.32 g, 67%). 1H NMR (400 MHz, DMSO-d6): δ 1.50-1.54 (m, 2H), 1.71-1.73 (m, 8H), 1.93-1.99 (m, 2H), 2.60 (s, 1H), 6.67 (d, J=8.4 Hz, 2H), 6.87 (d, J=8.5 Hz, 2H), 7.02 (d, J=8.5 Hz, 2H), 7.46 (d, J=8.3 Hz, 2H), 9.32 (s, 1H). In a 3-neck round-bottomed flask equipped with a reflux condenser and a nitrogen inlet The reaction mixture was heated at reflux for 2.5 h The reaction mixture was heated at reflux for 2 h The reaction mixture was filtered through a pad of Celite The pad of Celite was washed with EtOAc The filtrate was transferred to a separatory funnel the layers were separated The organic layer was washed with brine dried (MgSO4) filtered the filtrate was concentrated to give an oily residue purified by flash column chromatography

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

Procedure: In a 3-neck round-bottomed flask equipped with a reflux condenser and a nitrogen inlet, TiCl4 (0.51 mL, 4.67 mmol) was slowly added to a suspension of zinc powder (0.63 g, 9.60 mmol) in dry THF (13 mL) at room temperature. The reaction mixture was heated at reflux for 2.5 h. The reaction mixture was taken out of the oil bath and a solution of (4-bromophenyl)(4-hydroxyphenyl)methanone (2) (0.35 g, 1.26 mmol) and bicyclo[3.3.1]nonan-9-one (0.52 g, 3.79 mmol) in dry THF (13 mL) was added. The reaction mixture was heated at reflux for 2 h. The reaction mixture was allowed to cool at RT. Water (10 mL) was added to the reaction mixture via a syringe followed by 10% K2CO3 (10 mL). The reaction mixture was filtered through a pad of Celite. The pad of Celite was washed with EtOAc. The filtrate was transferred to a separatory funnel and the layers were separated. The organic layer was washed with brine, dried (MgSO4), filtered, and the filtrate was concentrated to give an oily residue. The crude product was adsorbed onto silica and purified by flash column chromatography using SiO2 and a hexanes:EtOAc gradient (100:0 to 75:25) to afford compound 43 as a white powder (0.32 g, 67%). 1H NMR (400 MHz, DMSO-d6): δ 1.50-1.54 (m, 2H), 1.71-1.73 (m, 8H), 1.93-1.99 (m, 2H), 2.60 (s, 1H), 6.67 (d, J=8.4 Hz, 2H), 6.87 (d, J=8.5 Hz, 2H), 7.02 (d, J=8.5 Hz, 2H), 7.46 (d, J=8.3 Hz, 2H), 9.32 (s, 1H). In a 3-neck round-bottomed flask equipped with a reflux condenser and a nitrogen inlet The reaction mixture was heated at reflux for 2.5 h The reaction mixture was heated at reflux for 2 h The reaction mixture was filtered through a pad of Celite The pad of Celite was washed with EtOAc The filtrate was transferred to a separatory funnel the layers were separated The organic layer was washed with brine dried (MgSO4) filtered the filtrate was concentrated to give an oily residue purified by flash column chromatography

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

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

Procedure: In a 3-neck round-bottomed flask equipped with a reflux condenser and a nitrogen inlet, TiCl4 (0.51 mL, 4.67 mmol) was slowly added to a suspension of zinc powder (0.63 g, 9.60 mmol) in dry THF (13 mL) at room temperature. The reaction mixture was heated at reflux for 2.5 h. The reaction mixture was taken out of the oil bath and a solution of (4-bromophenyl)(4-hydroxyphenyl)methanone (2) (0.35 g, 1.26 mmol) and bicyclo[3.3.1]nonan-9-one (0.52 g, 3.79 mmol) in dry THF (13 mL) was added. The reaction mixture was heated at reflux for 2 h. The reaction mixture was allowed to cool at RT. Water (10 mL) was added to the reaction mixture via a syringe followed by 10% K2CO3 (10 mL). The reaction mixture was filtered through a pad of Celite. The pad of Celite washed with EtOAc. The filtrate was transferred to a separatory funnel and the layers were separated. The organic layer washed with brine, dried (MgSO4), filtered, and the filtrate was concentrated to give an oily residue. The crude product was adsorbed onto silica and purified by flash column chromatography using SiO2 and a hexanes:EtOAc gradient (100:0 to 75:25) to afford compound 43 as a white powder (0.32 g, 67%). 1H NMR (400 MHz, DMSO-d6): δ 1.50-1.54 (m, 2H), 1.71-1.73 (m, 8H), 1.93-1.99 (m, 2H), 2.60 (s, 1H), 6.67 (d, J=8.4 Hz, 2H), 6.87 (d, J=8.5 Hz, 2H), 7.02 (d, J=8.5 Hz, 2H), 7.46 (d, J=8.3 Hz, 2H), 9.32 (s, 1H). In a 3-neck round-bottomed flask equipped with a reflux condenser and a nitrogen inlet The reaction mixture was heated at reflux for 2.5 h The reaction mixture was heated at reflux for 2 h The reaction mixture was filtered through a pad of Celite The pad of Celite washed with EtOAc The filtrate was transferred to a separatory funnel the layers were separated The organic layer washed with brine dried (MgSO4) filtered the filtrate was concentrated to give an oily residue purified by flash column chromatography

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 15.9 g of 9-borabicyclo [3.3.1] nonan, 14.8 g of n-pentylphenyldivinylsilane and 150 ml of n-hexane was refluxed for 2 hours and then cooled with ice water. 7.0 ml of borane-dimethylsufide was added to the mixture, which was then heated again and refluxed for 2 hours. After cooling, 16 ml of methanol was added at room temperature and the mixture was stirred for 2 hours at 0° C. 25.0 g of dichloromethylmethyl ether was then dripped into the mixture, followed by also dripping a hexane-tetrahydrofuran (1:1) solution of 1.33M lithium t-butoxide into the mixture. After stirring at room temperature for 2 hours, 80 ml of ethanol, 10 ml of water and 10.0 g of sodium hydroxide were added. Then 80 ml of an aqueous solution of 30% hydrogen peroxide was slowly added. After stirring at room temperature for 2 hours, the organic layer was dried/concentrated to obtain a mixture of the target product and bicyclo [3.3.1] nonan-9-one. They were separated by means of silica-gel chromatography to obtain 15.2 g (yield 91%) of the target product. The target product thus obtained exhibited the same spectra as those of Example 7. was refluxed for 2 hours was then heated again refluxed for 2 hours After cooling After stirring at room temperature for 2 hours After stirring at room temperature for 2 hours the organic layer was dried/concentrated to obtain They were separated by means of silica-gel chromatography