N-(2-Bromoethoxy)phthalimide

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 3-(4-piperidinyl)-6-fluorobenzisoxazole (3.42 g, 15 mmol), N-(2-bromoethoxy)-phthalimide (4,3 g, 16 mmol) and K2CO3 (26 g, 18 mmol) in acetonitrile (150 ml) was heated at reflux for 2 hours. The solids were removed and the solvent was evaporated. The residue was purified over a flash chromatography column (packed with SiO2, 60 g; eluted with dichloromethane (DCM) and 1% CH3OH in DCM). The pure product thus obtained, weighing 6.8 g was crystallized from DCM:ethanol. Recrystallization from ethanol and i-propyl ether yielded white crystals (2.4 g, m.p. 125-127° C.) as the hemihydrate. was heated at reflux for 2 hours The solids were removed the solvent was evaporated The residue was purified over a flash chromatography column (packed with SiO2, 60 g; eluted with dichloromethane (DCM) and 1% CH3OH in DCM) The pure product thus obtained was crystallized from DCM Recrystallization from ethanol and i-propyl ether yielded white crystals (2.4 g, m.p. 125-127° C.) as the hemihydrate

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 3-(4-piperidinyl)-6-fluorobenzisoxazole (3.42 g, 15 mmol), N-(2-bromoethoxy)-phthalimide (4.3 g, 16 mmol) and K2CO3 (26 g, 18 mmol) in acetonitrile (150 ml) was heated at reflux for 2 hours. The solids were removed and the solvent was evaporated. The residue was purified over a flash chromatography column (packed with SiO2, 60 g; eluted with dichloromethane (DCM) and 1% CH3OH in DCM). The pure product thus obtained, weighing 6.8 g was crystallized from DCM:ethanol. Recrystallization from ethanol and i-propyl ether yielded white crystals (2.4 g, m.p. 125°-127° C.) as the hemihydrate. was heated at reflux for 2 hours The solids were removed the solvent was evaporated The residue was purified over a flash chromatography column (packed with SiO2, 60 g; eluted with dichloromethane (DCM) and 1% CH3OH in DCM) The pure product thus obtained was crystallized from DCM Recrystallization from ethanol and i-propyl ether yielded white crystals (2.4 g, m.p. 125°-127° C.) as the hemihydrate

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 3-(4-piperidinyl)-6-fluorobenzisoxazole (3.42 g, 15 mmol), N-(2-bromoethoxy)-phthalimide (4.3 g, 16 mmol) and K2CO3 (26 g, 18 mmol) in acetonitrile (150 ml) was heated at reflux for 2 hours. The solids were removed and the solvent was evaporated. The residue was purified over a flash chromatography column (packed with SiO2, 60 g; eluted with dichloromethane (DCM) and 1% CH3OH in DCM). The pure product thus obtained, weighing 6.8 g was crystallized from DCM:ethanol. Recrystallization from ethanol and i-propyl ether yielded white crystals (2.4 g, m.p. 125°-127° C.) as the hemihydrate. was heated at reflux for 2 hours The solids were removed the solvent was evaporated The residue was purified over a flash chromatography column (packed with SiO2, 60 g; eluted with dichloromethane (DCM) and 1% CH3OH in DCM) The pure product thus obtained was crystallized from DCM Recrystallization from ethanol and i-propyl ether yielded white crystals (2.4 g, m.p. 125°-127° C.) as the hemihydrate

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 3-(4-piperidinyl)-6-fluorobenzisoxazole (3.42 g, 15 mmol), N-(2-bromoethoxy)-phthalimide (4.3 g, 16 mmol) and K2CO3 (26 g, 18 mmol) in acetonitrile (150 ml) was heated at reflux for 2 hours. The solids were removed and the solvent was evaporated. The residue was purified over a flash chromatography column (packed with SiO2, 60 g; eluted with dichloromethane (DCM) and 1% CH3OH in DCM). The pure product thus obtained, weighing 6.8 g was crystallized from DCM:ethanol. Recrystallization from ethanol and i-propyl ether yielded white crystals (2.4 g, m.p. 125°-127° C.) as the hemihydrate. was heated at reflux for 2 hours The solids were removed the solvent was evaporated The residue was purified over a flash chromatography column (packed with SiO2, 60 g; eluted with dichloromethane (DCM) and 1% CH3OH in DCM) The pure product thus obtained was crystallized from DCM Recrystallization from ethanol and i-propyl ether yielded white crystals (2.4 g, m.p. 125°-127° C.) as the hemihydrate

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 3-(4-piperidinyl)-6-fluorobenzisoxazole (3.42 g, 15 mmol), N-(2-bromoethoxy)-phthalimide (4.3 g, 16 mmol) and K2CO3 (26 g, 18 mmol) in acetonitrile (150 ml) was heated at reflux for 2 hours. The solids were removed and the solvent was evaporated. The residue was purified over a flash chromatography column (packed with SiO2, 60 g; eluted with dichloromethane (DCM) and 1% CH3OH in DCM). The pure product thus obtained, weighing 6.8 g was crystallized from DCM:ethanol. Recrystallization from ethanol and i-propyl ether yielded white crystals (2.4 g, m.p. 125°-127° C. as the hemihydrate. was heated at reflux for 2 hours The solids were removed the solvent was evaporated The residue was purified over a flash chromatography column (packed with SiO2, 60 g; eluted with dichloromethane (DCM) and 1% CH3OH in DCM) The pure product thus obtained was crystallized from DCM Recrystallization from ethanol and i-propyl ether yielded white crystals (2.4 g, m.p. 125°-127° C. as the hemihydrate

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 2-(2-Bromo-ethoxy)-isoindole-1,3-dione is prepared from 1,2-dibromoethane and N-hydroxyphthalimide as described in WO 00/18790, and is then subjected to the procedure in J. Org. Chem., 1963, 28, 1604 to yield the desired product.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: N-(2-Bromoethoxy)phthalimide was synthesised by a modification of the procedure of Bauer and Suresh (Bauer et al 1963). N-Hydroxyphthalimide (80 g, 0.49 mol), triethylamine (150 mL, 1.08 mol), and 1,2-dibromoethane (175 mL, 2.30 mol) were combined in DMF (575 mL) and stirred at room temperature overnight. Solids were filtered and washed with DMF and the filtrate was diluted with water (4.0 L) and the resulting precipitate filtered, dissolved in EtOAc (500 mL), and washed with 1 N HCl (2×100 mL), water (1×100 mL), and dried over MgSO4. Volatiles were removed in vacuo, and the resulting solid recrystallised from 95% EtOH to give (9) as a white solid (87.1 g, 70%): mp. 94-96° C.; lit. mp. 94-96° C. 1H NMR (CDCl3): δ 7.82 (m, 4H), 4.49 (t, 2H, J=6.9 Hz), 3.65 (t, 2H, J=6.9 Hz). Solids were filtered washed with DMF the filtrate was diluted with water (4.0 L) the resulting precipitate filtered dissolved in EtOAc (500 mL) washed with 1 N HCl (2×100 mL), water (1×100 mL) dried over MgSO4 Volatiles were removed in vacuo the resulting solid recrystallised from 95% EtOH

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 3-(4-piperidinyl)-6-fluorobenzisoxazole (3.42 g, 15 mmol), N-(2-bromoethoxy)-phthalimide (4.3 g, 16 mmol) and K2CO3 (26 g, 18 mmol) in acetonitrile (150 ml) was heated at reflux for 2 hours. The solids were removed and the solvent was evaporated. The residue was purified over a flash chromatography column (packed with SiO2, 60 g; eluted with dichloromethane (DCM) and 1% CH3OH in DCM). The pure product thus obtained, weighing 6.8 g was crystallized from DCM:ethanol. Recrystallization from ethanol and i-propyl ether yielded white crystals (2.4 g, m.p. 125-127° C.) as the hemihydrate. was heated at reflux for 2 hours The solids were removed the solvent was evaporated The residue was purified over a flash chromatography column (packed with SiO2, 60 g; eluted with dichloromethane (DCM) and 1% CH3OH in DCM) The pure product thus obtained was crystallized from DCM Recrystallization from ethanol and i-propyl ether yielded white crystals (2.4 g, m.p. 125-127° C.) as the hemihydrate

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 2-(2-Bromo-ethoxy)-isoindole-1,3-dione is prepared from 1,2-dibromoethane and N-hydroxyphthalimide as described in WO 00/18790, and is then subjected to the procedure in J. Org. Chem., 1963, 28, 1604 to yield the desired product.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 2-(2-Bromo-ethoxy)-isoindole-1,3-dione is prepared from 1,2-dibromoethane and N-hydroxyphthalimide as described in WO 00/18790, and is then subjected to the procedure in J. Org. Chem., 1963, 28, 1604 to yield the desired product.