3-bromo-1-methoxypyrrolidin-2-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: Triphenylphosphine (1.5 g, 5.7 mmol) is added to a solution of N-methoxy-3-bromopyrrolidin-2-one (Ikuta, et al. J. Med. Chem. 1984, 30, 1995) (1.0 g, 5.2 mmol) in THF (10 mL) and the mixture is warmed to reflux under an argon atmosphere for 12 hours. The reaction mixture is cooled in an ice bath and the solvent is decanted away from the resulting solid. The solid is added to a solution of triethylamine (0.93 g, 9.3 mmol) and 4,6-bis-(1,1-dimethylethyl)-5-hydroxypyrimidine-2-carboxaldehyde (0.97 g, 4.1 mmol) in ethanol (10 mL). The resulting mixture is warmed to reflux for 3 hours under an argon atmosphere. The mixture is cooled to room temperature, the EtOH is evaporated and the residue is partitioned between 50 mL EtOAc and 50 mL H2O. The organic extract is dried over MgSO4. The solvent is evaporated and the solid is recrystallized from Et2O/hexane. Yield of 3-[[4,6-bis-(1,1-dimethylethyl)-5-hydroxy-2-pyrimidinyl]methylene]-N-methoxypyrrolidin-2-one=0.34 g (20%), mp 184°-186° C. the mixture is warmed to reflux under an argon atmosphere for 12 hours The reaction mixture is cooled in an ice bath the solvent is decanted away from the resulting solid The resulting mixture is warmed to reflux for 3 hours under an argon atmosphere the EtOH is evaporated the residue is partitioned between 50 mL EtOAc and 50 mL H2O The organic extract is dried over MgSO4 The solvent is evaporated the solid is recrystallized from Et2O/hexane

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

実験手順: 130 g of the above-obtained oil containing N-methoxy-2,4-dibromobutyric acid amide were dissolved in 500 mL of benzene. To the resultant solution, 12 g of sodium hydride were gradually added while cooling the solution to 15° C. to 20° C. After the completion of the addition, ice was added to the resultant reaction solution to decompose excessive sodium hydride. The resultant solution was washed with a saturated saline, followed by drying the solution by magnesium sulfate. The solution was concentrated under a reduced pressure and purified by silica gel-acetone/benzene column chromatography. Consequently, 39 g (0.2 mol) of N-methoxy-2-bromo-4-butyrolactam (with a yield of 36% from 2,4-dibromobutyric acid bromide) was obtained. while cooling the solution to 15° C. to 20° C After the completion of the addition, ice was added to the resultant reaction solution The resultant solution was washed with a saturated saline by drying the solution by magnesium sulfate The solution was concentrated under a reduced pressure purified by silica gel-acetone/benzene column chromatography

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

実験手順: 130 g of the above-obtained oil containing N-methoxy-2,4-dibromobutyric acid amide were dissolved in 500 mL of benzene. To the resultant solution, 12 g of sodium hydride were gradually added while cooling the solution to 15° C. to 20° C. After the completion of the addition, ice was added to the resultant reaction solution to decompose excessive sodium hydride. The resultant solution was washed with a saturated saline, followed by drying the solution by magnesium sulfate. The solution was concentrated under a reduced pressure and purified by silica gel-acetone/benzene column chromatography. Consequently, 39 g (0.2 mol) of N-methoxy-2-bromo-4-butyrolactam (with a yield of 36% from 2,4-dibromobutyric acid bromide) was obtained. while cooling the solution to 15° C. to 20° C After the completion of the addition, ice was added to the resultant reaction solution The resultant solution was washed with a saturated saline by drying the solution by magnesium sulfate The solution was concentrated under a reduced pressure purified by silica gel-acetone/benzene column chromatography

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

実験手順: Triphenylphosphine (1.5 g, 5.7 mmol) is added to a solution of N-methoxy-3-bromopyrrolidin-2-one (Ikuta, et al. J. Med. Chem. 1984, 30, 1995) (1.0 g, 5.2 mmol) in THF (10 mL) and the mixture is warmed to reflux under an argon atmosphere for 12 hours. The reaction mixture is cooled in an ice bath and the solvent is decanted away from the resulting solid. The solid is added to a solution of triethylamine (0.93 g, 9.3 mmol) and 4,6-bis-(1,1-dimethylethyl)-5-hydroxypyrimidine-2-carboxaldehyde (0.97 g, 4.1 mmol) in ethanol (10 mL). The resulting mixture is warmed to reflux for 3 hours under an argon atmosphere. The mixture is cooled to room temperature, the EtOH is evaporated and the residue is partitioned between 50 mL EtOAc and 50 mL H2O. The organic extract is dried over MgSO4. The solvent is evaporated and the solid is recrystallized from Et2O/hexane. Yield of 3-[[4,6-bis-(1,1-dimethylethyl)-5-hydroxy-2-pyrimidinyl]methylene]-N-methoxypyrrolidin-2-one=0.34 g (20%), mp 184°-186° C. the mixture is warmed to reflux under an argon atmosphere for 12 hours The reaction mixture is cooled in an ice bath the solvent is decanted away from the resulting solid The resulting mixture is warmed to reflux for 3 hours under an argon atmosphere the EtOH is evaporated the residue is partitioned between 50 mL EtOAc and 50 mL H2O The organic extract is dried over MgSO4 The solvent is evaporated the solid is recrystallized from Et2O/hexane

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

実験手順: Triphenylphosphine (1.5 g, 5.7 mmol) is added to a solution of N-methoxy-3-bromopyrrolidin-2-one (Ikuta, et al. J. Med. Chem. 1984, 30, 1995) (1.0 g, 5.2 mmol) in THF (10 mL) and the mixture is warmed to reflux under an argon atmosphere for 12 hours. The reaction mixture is cooled in an ice bath and the solvent is decanted away from the resulting solid. The solid is added to a solution of triethylamine (0.93 g, 9.3 mmol) and 4,6-bis-(1,1-dimethylethyl)-5-hydroxypyrimidine-2-carboxaldehyde (0.97 g, 4.1 mmol) in ethanol (10 mL). The resulting mixture is warmed to reflux for 3 hours under an argon atmosphere. The mixture is cooled to room temperature, the EtOH is evaporated and the residue is partitioned between 50 mL EtOAc and 50 mL H2O. The organic extract is dried over MgSO4. The solvent is evaporated and the solid is recrystallized from Et2O/hexane. Yield of 3-[[4,6-bis-(1,1-dimethylethyl)-5-hydroxy-2-pyrimidinyl]methylene]-N-methoxypyrrolidin-2-one=0.34 g (20%), mp 184°-186° C. the mixture is warmed to reflux under an argon atmosphere for 12 hours The reaction mixture is cooled in an ice bath the solvent is decanted away from the resulting solid The resulting mixture is warmed to reflux for 3 hours under an argon atmosphere the EtOH is evaporated the residue is partitioned between 50 mL EtOAc and 50 mL H2O The organic extract is dried over MgSO4 The solvent is evaporated the solid is recrystallized from Et2O/hexane

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: Triphenylphosphine (1.5 g, 5.7 mmol) is added to a solution of N-methoxy-3-bromopyrrolidin-2-one (Ikuta, et al. J. Med. Chem. 1984, 30, 1995) (1.0 g, 5.2 mmol) in THF (10 mL) and the mixture is warmed to reflux under an argon atmosphere for 12 hours. The reaction mixture is cooled in an ice bath and the solvent is decanted away from the resulting solid. The solid is added to a solution of triethylamine (0.93 g, 9.3 mmol) and 4,6-bis-(1,1-dimethylethyl)-5-hydroxypyrimidine-2-carboxaldehyde (0.97 g, 4.1 mmol) in ethanol (10 mL). The resulting mixture is warmed to reflux for 3 hours under an argon atmosphere. The mixture is cooled to room temperature, the EtOH is evaporated and the residue is partitioned between 50 mL EtOAc and 50 mL H2O. The organic extract is dried over MgSO4. The solvent is evaporated and the solid is recrystallized from Et2O/hexane. Yield of 3-[[4,6-bis-(1,1-dimethylethyl)-5-hydroxy-2-pyrimidinyl]methylene]-N-methoxypyrrolidin-2-one=0.34 g (20%), mp 184°-186° C. the mixture is warmed to reflux under an argon atmosphere for 12 hours The reaction mixture is cooled in an ice bath the solvent is decanted away from the resulting solid The resulting mixture is warmed to reflux for 3 hours under an argon atmosphere the EtOH is evaporated the residue is partitioned between 50 mL EtOAc and 50 mL H2O The organic extract is dried over MgSO4 The solvent is evaporated the solid is recrystallized from Et2O/hexane

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

実験手順: A mixture of 75 g of N-methoxy-3-bromo-2-pyrrolidone, 105 g of triphenylphosphine and 700 ml of tetrahydrofuran was heated and refluxed for 24 hours. After cooled, the resulting precipitates were taken with filtration and washed with tetrahydrofuran. Dried, 54 g of the title compound 5 was obtained. was heated refluxed for 24 hours After cooled the resulting precipitates were taken with filtration washed with tetrahydrofuran Dried

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

実験手順: 1400 g of a crude N-methoxy-2,4-dibromobutanamide was dissolved in 5 liters of benzene. Then 125 g of NaH was added little by little to the solution at 15° to 20° C. while the reaction mixture was cooled with an iced water bath. After the reaction, the remaining NaH was decomposed with ice and the product mixture was washed with a saturated, aqueous salt solution. It was dried with magnesium sulfate. Then benzene was distilled out. The product was purified with the column chromatography, using silica gel and a mixture of acetaone and benzene to obtain 500 g of the title compound 4. was cooled with an iced water bath After the reaction the product mixture was washed with a saturated, aqueous salt solution It was dried with magnesium sulfate Then benzene was distilled out The product was purified with the column chromatography a mixture of acetaone and benzene

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

実験手順: 130 g of the above-obtained oil containing N-methoxy-2,4-dibromobutyric acid amide were dissolved in 500 mL of benzene. To the resultant solution, 12 g of sodium hydride were gradually added while cooling the solution to 15° C. to 20° C. After the completion of the addition, ice was added to the resultant reaction solution to decompose excessive sodium hydride. The resultant solution was washed with a saturated saline, followed by drying the solution by magnesium sulfate. The solution was concentrated under a reduced pressure and purified by silica gel-acetone/benzene column chromatography. Consequently, 39 g (0.2 mol) of N-methoxy-2-bromo-4-butyrolactam (with a yield of 36% from 2,4-dibromobutyric acid bromide) was obtained. while cooling the solution to 15° C. to 20° C After the completion of the addition, ice was added to the resultant reaction solution The resultant solution was washed with a saturated saline by drying the solution by magnesium sulfate The solution was concentrated under a reduced pressure purified by silica gel-acetone/benzene column chromatography