4-piperidin-1-ylbutan-1-ol

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

Procedure: 382 mg of sodium hydride (60% in suspension in oil) are added in small portions, over two hours, to a solution of 4-piperidin-1-ylbutan-1-ol in 10 mL of DMF, cooled to 0° C. with an ice bath. A solution of 4,5-difluoro-2-nitroaniline in 5 mL of N,N-dimethylformamide is then added dropwise. The medium is stirred at ambient temperature for 24 hours. 60 mL of distilled water are added and the reaction medium is extracted with 3×30 mL of ethyl acetate. The combined organic phases are dried over magnesium sulfate, filtered and concentrated under vacuum in a rotary evaporator. The reaction crude is purified by flash chromatography on an Intelliflash apparatus with an Analogix RS-12 silica cartridge, with a 100% to 85/15 dichloromethane/-methanol elution gradient. 700 mg of 4-fluoro-2-nitro-5-(4-piperidin-1-ylbutoxy)phenylamine are isolated in the form of a red oil. 1H NMR (300 MHz, DMSO-d6, δ in ppm): from 1.29 to 1.62 (m, 8H); 1.75 (m, 2H); 2.28 (m, 6H); 4.07 (t, J=6.5 Hz, 2H); 6.62 (d, J=7.5 Hz, 1H); 7.48 (broad s, 2H); 7.74 (d, J=12.0 Hz, 1H). the reaction medium is extracted with 3×30 mL of ethyl acetate The combined organic phases are dried over magnesium sulfate filtered concentrated under vacuum in a rotary evaporator The reaction crude is purified by flash chromatography on an Intelliflash apparatus with an Analogix RS-12 silica cartridge, with a 100% to 85/15 dichloromethane/-methanol elution gradient

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

Procedure: 11.68 mL of a 1M solution of lithium aluminum hydride in ether are added to 10 mL of tetrahydrofuran, and then 1 g of 4-piperidin-1-ylbutyric acid hydrochloride (synthesized according to a method described in the literature) is added. The medium is brought to boiling for approximately 10 minutes. After a return to ambient temperature and cooling to 0° C., a mixture of 1 mL of distilled water-30 mL of tetrahydrofuran is added dropwise. A large amount of gas is given off and strong exothermia is observed. After a return to ambient temperature, the medium is evaporated to dryness under reduced pressure in a rotary evaporator. The reaction crude is triturated in 150 mL of ethyl acetate and filtered, and the filtrate is washed with 2×20 mL of distilled water. The organic phase is dried over magnesium sulfate, filtered and then concentrated under vacuum in a rotary evaporator. 646 mg of 4-piperidin-1-ylbutan-1-ol are isolated in the form of a colorless oil. 1H NMR (300 MHz, DMSO-d6, δ in ppm): from 1.30 to 1.53 (m, 10H); 2.20 (t, J=6.5 Hz, 2H); 2.28 (m, 4H); 3.37 (broad t, J=6.5 Hz, 2H); 4.57 (broad s, 1H). is added is added dropwise After a return to ambient temperature, the medium is evaporated to dryness under reduced pressure in a rotary evaporator The reaction crude is triturated in 150 mL of ethyl acetate filtered the filtrate is washed with 2×20 mL of distilled water The organic phase is dried over magnesium sulfate filtered concentrated under vacuum in a rotary evaporator

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

Procedure: 11.68 mL of a 1M solution of lithium aluminum hydride in ether are added to 10 mL of tetrahydrofuran, and then 1 g of 4-piperidin-1-ylbutyric acid hydrochloride (synthesized according to a method described in the literature) is added. The medium is brought to boiling for approximately 10 minutes. After a return to ambient temperature and cooling to 0° C., a mixture of 1 mL of distilled water-30 mL of tetrahydrofuran is added dropwise. A large amount of gas is given off and strong exothermia is observed. After a return to ambient temperature, the medium is evaporated to dryness under reduced pressure in a rotary evaporator. The reaction crude is triturated in 150 mL of ethyl acetate and filtered, and the filtrate is washed with 2×20 mL of distilled water. The organic phase is dried over magnesium sulfate, filtered and then concentrated under vacuum in a rotary evaporator. 646 mg of 4-piperidin-1-ylbutan-1-ol are isolated in the form of a colorless oil. 1H NMR (300 MHz, DMSO-d6, δ in ppm): from 1.30 to 1.53 (m, 10H); 2.20 (t, J=6.5 Hz, 2H); 2.28 (m, 4H); 3.37 (broad t, J=6.5 Hz, 2H); 4.57 (broad s, 1H). is added is added dropwise After a return to ambient temperature, the medium is evaporated to dryness under reduced pressure in a rotary evaporator The reaction crude is triturated in 150 mL of ethyl acetate filtered the filtrate is washed with 2×20 mL of distilled water The organic phase is dried over magnesium sulfate filtered concentrated under vacuum in a rotary evaporator

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

Procedure: 11.68 mL of a 1M solution of lithium aluminum hydride in ether are added to 10 mL of tetrahydrofuran, and then 1 g of 4-piperidin-1-ylbutyric acid hydrochloride (synthesized according to a method described in the literature) is added. The medium is brought to boiling for approximately 10 minutes. After a return to ambient temperature and cooling to 0° C., a mixture of 1 mL of distilled water-30 mL of tetrahydrofuran is added dropwise. A large amount of gas is given off and strong exothermia is observed. After a return to ambient temperature, the medium is evaporated to dryness under reduced pressure in a rotary evaporator. The reaction crude is triturated in 150 mL of ethyl acetate and filtered, and the filtrate is washed with 2×20 mL of distilled water. The organic phase is dried over magnesium sulfate, filtered and then concentrated under vacuum in a rotary evaporator. 646 mg of 4-piperidin-1-ylbutan-1-ol are isolated in the form of a colorless oil. 1H NMR (300 MHz, DMSO-d6, δ in ppm): from 1.30 to 1.53 (m, 10H); 2.20 (t, J=6.5 Hz, 2H); 2.28 (m, 4H); 3.37 (broad t, J=6.5 Hz, 2H); 4.57 (broad s, 1H). is added is added dropwise After a return to ambient temperature, the medium is evaporated to dryness under reduced pressure in a rotary evaporator The reaction crude is triturated in 150 mL of ethyl acetate filtered the filtrate is washed with 2×20 mL of distilled water The organic phase is dried over magnesium sulfate filtered concentrated under vacuum in a rotary evaporator