4-azido-1-phenylbutan-1-one

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

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

Procedure: 4-Azidobutyrophenone (100.0 mg, 0.53 mmol) was dissolved in toluene (5 ml) at room temperature, and thereto were added ethylene glycol (0.06 ml, 1.06 mmol) and p-toluene sulfonic acid mono hydrate (10.1 mg, 0.05 mmol) in sequential order at the same temperature, and thereafter, the mixture was refluxed using a Dean Stark tube for 24 hours. The reaction solution was cooled to room temperature and added to water thereafter, followed by the extraction using ethyl acetate. The extracted organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The target compound was thus obtained as a colorless oil (133 mg). the mixture was refluxed for 24 hours followed by the extraction The extracted organic layer was washed with brine dried over anhydrous sodium sulfate concentrated under reduced pressure

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Chlorobutyrophenone (300.0 mg, 1.64 mmol) was dissolved in N,N-dimethylformamide (20 ml) at room tempaerature and then added to sodium azide (1.07 g, 16.42 mmol) at the same temperature, and thereafter stirred at 100° C. for 24 hours. The reaction solution was added to a saturated aqueous sodium hydrogencarbonate solution and then extracted by ethyl acetate, to obtain an organic layer. The extracted organic layer was washed with water and brine sequentially, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resultant saubstance was purified by silica gel column chromatography (n-hexane/ethyl acetate=5/1), whereby the target compound was obtained as a colorless oil (285.5 mg, 91.9%) extracted by ethyl acetate to obtain an organic layer The extracted organic layer was washed with water and brine sequentially dried over anhydrous sodium sulfate concentrated under reduced pressure The resultant saubstance was purified by silica gel column chromatography (n-hexane/ethyl acetate=5/1), whereby the target compound

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

Procedure: To a solution of 5-chloro-2-methylbenzohydrazide (2.70 g, 14.62 mmol) prepared as in Example 1, Step B, in toluene (100 mL) was added 4-azido-1-phenylbutan-1-one (3.04 g, 16.1 mmol) prepared as in Example 70, Step A, followed by p-toluenesulfonic acid monohydrate (0.28 g, 1.46 mmol). The reaction was heated to reflux and stirred under a Dean-Stark trap for 16 hours. The cooled mixture was diluted with EtOAc (300 mL) and washed with NaHCO3 (100 mL). The aqueous layer was extracted with EtOAc (100 mL) and the combined organics were washed with brine (100 mL), dried over Na2SO4 and concentrated. The residue was triturated with ether and filtered to afford the product (3.09 g, 59%) as a tan solid. The reaction was heated to reflux washed with NaHCO3 (100 mL) The aqueous layer was extracted with EtOAc (100 mL) the combined organics were washed with brine (100 mL) dried over Na2SO4 concentrated The residue was triturated with ether filtered

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

Procedure: To a solution of 2,5-difluorobenzothiohydrazide (1.5 g, 7.97 mmol) in EtOH/dichloromethane (3:1, 16 mL) was added 4-azido-1-phenylbutan-1-one (1.36 g, 7.17 mmol). After stirring at room temperature for 16 hours, acetic acid (2 drops) was added and the mixture was stirred for another 16 hours. The reaction mixture was then concentrated under reduced pressure and chromatographed (9:1 hexanes/ethyl acetate) to provide the product (1.41 g, 41%) as a bright yellow syrup. the mixture was stirred for another 16 hours The reaction mixture was then concentrated under reduced pressure chromatographed (9:1 hexanes/ethyl acetate)

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

Procedure: To a solution of 2,5-difluorobenzothiohydrazide (1.5 g, 7.97 mmol) in EtOH/dichloromethane (3:1, 16 mL) was added 4-azido-1-phenylbutan-1-one (1.36 g, 7.17 mmol). After stirring at room temperature for 16 hours, acetic acid (2 drops) was added and the mixture was stirred for another 16 hours. The reaction mixture was then concentrated under reduced pressure and chromatographed (9:1 hexanes/ethyl acetate) to provide the product (1.41 g, 41%) as a bright yellow syrup. the mixture was stirred for another 16 hours The reaction mixture was then concentrated under reduced pressure chromatographed (9:1 hexanes/ethyl acetate)

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-chloro-1-phenylbutan-1-one (26.4 mL, 164 mmol) in DMSO (200 mL) was added sodium azide (12.8 g, 197 mmol). The solution was warmed to 55° C. and stirred for 16 hours. The cooled mixture was then treated with water (600 mL) and extracted with ether (3×200 mL). The combined organics were washed with water (8×100 mL) and brine (100 mL) then dried over MgSO4 and concentrated to provide the product as an orange oil (30.7 g, 99%). extracted with ether (3×200 mL) The combined organics were washed with water (8×100 mL) and brine (100 mL) then dried over MgSO4 concentrated

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-chloro-1-phenylbutan-1-one (26.4 mL, 164 mmol) in DMSO (200 mL) was added sodium azide (12.8 g, 197 mmol). The solution was warmed to 55° C. and stirred for 16 hours. The cooled mixture was then treated with water (600 mL) and extracted with ether (3×200 mL). The combined organics were washed with water (8×100 mL) and brine (100 mL) then dried over MgSO4 and concentrated to provide the product as an orange oil (30.7 g, 99%). extracted with ether (3×200 mL) The combined organics were washed with water (8×100 mL) and brine (100 mL) then dried over MgSO4 concentrated

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

Procedure: To a solution of 5-chloro-2-methylbenzohydrazide (2.70 g, 14.62 mmol) prepared as in Example 1, Step B, in toluene (100 mL) was added 4-azido-1-phenylbutan-1-one (3.04 g, 16.1 mmol) prepared as in Example 70, Step A, followed by p-toluenesulfonic acid monohydrate (0.28 g, 1.46 mmol). The reaction was heated to reflux and stirred under a Dean-Stark trap for 16 hours. The cooled mixture was diluted with EtOAc (300 mL) and washed with NaHCO3 (100 mL). The aqueous layer was extracted with EtOAc (100 mL) and the combined organics were washed with brine (100 mL), dried over Na2SO4 and concentrated. The residue was triturated with ether and filtered to afford the product (3.09 g, 59%) as a tan solid. The reaction was heated to reflux washed with NaHCO3 (100 mL) The aqueous layer was extracted with EtOAc (100 mL) the combined organics were washed with brine (100 mL) dried over Na2SO4 concentrated The residue was triturated with ether filtered

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

Procedure: To a solution of 2,5-difluorobenzothiohydrazide (1.5 g, 7.97 mmol) in EtOH/dichloromethane (3:1, 16 mL) was added 4-azido-1-phenylbutan-1-one (1.36 g, 7.17 mmol). After stirring at room temperature for 16 hours, acetic acid (2 drops) was added and the mixture was stirred for another 16 hours. The reaction mixture was then concentrated under reduced pressure and chromatographed (9:1 hexanes/ethyl acetate) to provide the product (1.41 g, 41%) as a bright yellow syrup. the mixture was stirred for another 16 hours The reaction mixture was then concentrated under reduced pressure chromatographed (9:1 hexanes/ethyl acetate)

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-chloro-1-phenylbutan-1-one (26.4 mL, 164 mmol) in DMSO (200 mL) was added sodium azide (12.8 g, 197 mmol). The solution was warmed to 55° C. and stirred for 16 hours. The cooled mixture was then treated with water (600 mL) and extracted with ether (3×200 mL). The combined organics were washed with water (8×100 mL) and brine (100 mL) then dried over MgSO4 and concentrated to provide the product as an orange oil (30.7 g, 99%). extracted with ether (3×200 mL) The combined organics were washed with water (8×100 mL) and brine (100 mL) then dried over MgSO4 concentrated

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

Procedure: To a solution of 5-chloro-2-methylbenzohydrazide (2.70 g, 14.62 mmol) prepared as in Example 1, Step B, in toluene (100 mL) was added 4-azido-1-phenylbutan-1-one (3.04 g, 16.1 mmol) prepared as in Example 70, Step A, followed by p-toluenesulfonic acid monohydrate (0.28 g, 1.46 mmol). The reaction was heated to reflux and stirred under a Dean-Stark trap for 16 hours. The cooled mixture was diluted with EtOAc (300 mL) and washed with NaHCO3 (100 mL). The aqueous layer was extracted with EtOAc (100 mL) and the combined organics were washed with brine (100 mL), dried over Na2SO4 and concentrated. The residue was triturated with ether and filtered to afford the product (3.09 g, 59%) as a tan solid. The reaction was heated to reflux washed with NaHCO3 (100 mL) The aqueous layer was extracted with EtOAc (100 mL) the combined organics were washed with brine (100 mL) dried over Na2SO4 concentrated The residue was triturated with ether filtered