ethyl 4-methyl-2,3-dihydro-1,4-benzoxazine-2-carboxylate

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a sealable vessel, potassium carbonate (56 mg, 0.41 mmol) was added to a solution of (±)-ethyl 3,4-dihydro-2H-benzo[b][1,4]oxazine-2-carboxylate (60 mg, 0.29 mmol) and iodomethane (22 □L, 0.35 mmol) in acetone (2 mL). The vessel was sealed and the reaction mixture was stirred at 60° C. for 24 h. The mixture was cooled to ambient temperature, diluted with dichloromethane (60 mL), and the organic layer was extracted with water (10 mL) and half-saturated brine (10 mL). The organic layer was dried over sodium sulfate and concentrated. Purification of the concentrate by flash column chromatography (5% to 10% EtOAc/hexane) afforded the title compound (43 mg, 0.19 mmol). MS m/z: 222 (M+1). The vessel was sealed The mixture was cooled to ambient temperature the organic layer was extracted with water (10 mL) and half-saturated brine (10 mL) The organic layer was dried over sodium sulfate concentrated Purification of the concentrate by flash column chromatography (5% to 10% EtOAc/hexane)

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a sealable vessel, potassium carbonate (56 mg, 0.41 mmol) was added to a solution of (±)-ethyl 3,4-dihydro-2H-benzo[b][1,4]oxazine-2-carboxylate (60 mg, 0.29 mmol) and iodomethane (22 □L, 0.35 mmol) in acetone (2 mL). The vessel was sealed and the reaction mixture was stirred at 60° C. for 24 h. The mixture was cooled to ambient temperature, diluted with dichloromethane (60 mL), and the organic layer was extracted with water (10 mL) and half-saturated brine (10 mL). The organic layer was dried over sodium sulfate and concentrated. Purification of the concentrate by flash column chromatography (5% to 10% EtOAc/hexane) afforded the title compound (43 mg, 0.19 mmol). MS m/z: 222 (M+1). The vessel was sealed The mixture was cooled to ambient temperature the organic layer was extracted with water (10 mL) and half-saturated brine (10 mL) The organic layer was dried over sodium sulfate concentrated Purification of the concentrate by flash column chromatography (5% to 10% EtOAc/hexane)

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

実験手順: 1.6 mmol (0.1 ml) of acetyl chloride and 4 mmol (545 mg) of aluminum chloride are added to a solution of 1.6 mmol (355 mg) of 2-ethoxycarbonyl-4-methyl-3,4-dihydro-2H-1,4-benzoxazine (described in J. Heterocyclic Chem., 1985, 22, 177) in 18 ml of dichloromethane at -10° C. The reaction mixture is stirred at room temperature for 1 hour before being hydrolysed by a cooled aqueous solution of 2 M hydrochloric acid. The mixture is extracted with dichloromethane and the organic phase is washed with a saturated solution of NaHCO3, dried over magnesium sulphate, concentrated and purified by chromatography on silica gel using a petroleum ether/ethyl acetate mixture (7/3) as eluant to yield the expected product. The mixture is extracted with dichloromethane the organic phase is washed with a saturated solution of NaHCO3 dried over magnesium sulphate concentrated purified by chromatography on silica gel using a petroleum ether/ethyl acetate mixture (7/3) as eluant

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

実験手順: 2,4-Dimethyl-2-methoxycarbonyl-3,4-dihydro-2H-1,4-benzoxazine 20 ml of 5% KOH are added to 11.3 mmol (2.5 g) of 2-ethoxycarbonyl-4-methyl-3,4-dihydro-2H-1,4-benzoxazine (described in J. Heterocyclic Chem., 1985, 22, 177) in 10 ml of ethanol and 10 ml of tetrahydrofuran. The reaction mixture is stirred at room temperature for 1 hour. The solvent is evaporated off, and the resulting residue is taken up in an ethyl acetate/water mixture, at acidic pH, and extracted. The organic phase is dried and concentrated. The residue is then dissolved in 90 ml of tetrahydrofuran and the temperature is reduced to -50° C. before the addition of 45.2 mmol (22.6 ml) of lithium diisopropylamide as a 2M solution in tetrahydrofuran. The reaction mixture is stirred for 2 hours at -50° C., and then 45.2 mmol (2.7 ml) of iodomethane are added and the temperature is brought back up to 25° C. in the course of 2 hours. After hydrolysis, the mixture is acidified to pH=4 and extracted with ethyl acetate. The organic phase is dried and concentrated. The residue is then dissolved in 150 ml of methanol in the presence of para-toluenesulphonic acid. The reaction mixture is heated at reflux for 18 hours. The solvent is evaporated off, and the mixture is taken up in an ethyl acetate/water mixture and extracted. The organic phase is dried, concentrated and purified by chromatography on silica gel using an ethyl acetate/petroleum ether mixture (3/7) as eluant to yield the expected compound. The solvent is evaporated off extracted The organic phase is dried concentrated The residue is then dissolved in 90 ml of tetrahydrofuran The reaction mixture is stirred for 2 hours at -50° C. is brought back up to 25° C. in the course of 2 hours After hydrolysis extracted with ethyl acetate The organic phase is dried concentrated The residue is then dissolved in 150 ml of methanol in the presence of para-toluenesulphonic acid The reaction mixture is heated at reflux for 18 hours The solvent is evaporated off extracted The organic phase is dried concentrated purified by chromatography on silica gel using an ethyl acetate/petroleum ether mixture (3/7) as eluant

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

実験手順: 2,4-Dimethyl-2-methoxycarbonyl-3,4-dihydro-2H-1,4-benzoxazine 20 ml of 5% KOH are added to 11.3 mmol (2.5 g) of 2-ethoxycarbonyl-4-methyl-3,4-dihydro-2H-1,4-benzoxazine (described in J. Heterocyclic Chem., 1985, 22, 177) in 10 ml of ethanol and 10 ml of tetrahydrofuran. The reaction mixture is stirred at room temperature for 1 hour. The solvent is evaporated off, and the resulting residue is taken up in an ethyl acetate/water mixture, at acidic pH, and extracted. The organic phase is dried and concentrated. The residue is then dissolved in 90 ml of tetrahydrofuran and the temperature is reduced to -50° C. before the addition of 45.2 mmol (22.6 ml) of lithium diisopropylamide as a 2M solution in tetrahydrofuran. The reaction mixture is stirred for 2 hours at -50° C., and then 45.2 mmol (2.7 ml) of iodomethane are added and the temperature is brought back up to 25° C. in the course of 2 hours. After hydrolysis, the mixture is acidified to pH=4 and extracted with ethyl acetate. The organic phase is dried and concentrated. The residue is then dissolved in 150 ml of methanol in the presence of para-toluenesulphonic acid. The reaction mixture is heated at reflux for 18 hours. The solvent is evaporated off, and the mixture is taken up in an ethyl acetate/water mixture and extracted. The organic phase is dried, concentrated and purified by chromatography on silica gel using an ethyl acetate/petroleum ether mixture (3/7) as eluant to yield the expected compound. The solvent is evaporated off extracted The organic phase is dried concentrated The residue is then dissolved in 90 ml of tetrahydrofuran The reaction mixture is stirred for 2 hours at -50° C. is brought back up to 25° C. in the course of 2 hours After hydrolysis extracted with ethyl acetate The organic phase is dried concentrated The residue is then dissolved in 150 ml of methanol in the presence of para-toluenesulphonic acid The reaction mixture is heated at reflux for 18 hours The solvent is evaporated off extracted The organic phase is dried concentrated purified by chromatography on silica gel using an ethyl acetate/petroleum ether mixture (3/7) as eluant

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a sealable vessel, potassium carbonate (56 mg, 0.41 mmol) was added to a solution of (±)-ethyl 3,4-dihydro-2H-benzo[b][1,4]oxazine-2-carboxylate (60 mg, 0.29 mmol) and iodomethane (22 □L, 0.35 mmol) in acetone (2 mL). The vessel was sealed and the reaction mixture was stirred at 60° C. for 24 h. The mixture was cooled to ambient temperature, diluted with dichloromethane (60 mL), and the organic layer was extracted with water (10 mL) and half-saturated brine (10 mL). The organic layer was dried over sodium sulfate and concentrated. Purification of the concentrate by flash column chromatography (5% to 10% EtOAc/hexane) afforded the title compound (43 mg, 0.19 mmol). MS m/z: 222 (M+1). The vessel was sealed The mixture was cooled to ambient temperature the organic layer was extracted with water (10 mL) and half-saturated brine (10 mL) The organic layer was dried over sodium sulfate concentrated Purification of the concentrate by flash column chromatography (5% to 10% EtOAc/hexane)

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a sealable vessel, potassium carbonate (56 mg, 0.41 mmol) was added to a solution of (±)-ethyl 3,4-dihydro-2H-benzo[b][1,4]oxazine-2-carboxylate (60 mg, 0.29 mmol) and iodomethane (22 L, 0.35 mmol) in acetone (2 mL). The vessel was sealed and the reaction mixture was stirred at 60° C. for 24 h. The mixture was cooled to ambient temperature, diluted with dichloromethane (60 mL), and the organic layer was extracted with water (10 mL) and half-saturated brine (10 mL). The organic layer was dried over sodium sulfate and concentrated. Purification of the concentrate by flash column chromatography (5% to 10% EtOAc/hexane) afforded the title compound (43 mg, 0.19 mmol). MS m/z: 222 (M+1). The vessel was sealed The mixture was cooled to ambient temperature the organic layer was extracted with water (10 mL) and half-saturated brine (10 mL) The organic layer was dried over sodium sulfate concentrated Purification of the concentrate by flash column chromatography (5% to 10% EtOAc/hexane)

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

実験手順: 1.6 mmol (0.1 ml) of acetyl chloride and 4 mmol (545 mg) of aluminum chloride are added to a solution of 1.6 mmol (355 mg) of 2-ethoxycarbonyl-4-methyl-3,4-dihydro-2H-1,4-benzoxazine (described in J. Heterocyclic Chem., 1985, 22, 177) in 18 ml of dichloromethane at -10° C. The reaction mixture is stirred at room temperature for 1 hour before being hydrolysed by a cooled aqueous solution of 2 M hydrochloric acid. The mixture is extracted with dichloromethane and the organic phase is washed with a saturated solution of NaHCO3, dried over magnesium sulphate, concentrated and purified by chromatography on silica gel using a petroleum ether/ethyl acetate mixture (7/3) as eluant to yield the expected product. The mixture is extracted with dichloromethane the organic phase is washed with a saturated solution of NaHCO3 dried over magnesium sulphate concentrated purified by chromatography on silica gel using a petroleum ether/ethyl acetate mixture (7/3) as eluant

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

実験手順: 2,4-Dimethyl-2-methoxycarbonyl-3,4-dihydro-2H-1,4-benzoxazine 20 ml of 5% KOH are added to 11.3 mmol (2.5 g) of 2-ethoxycarbonyl-4-methyl-3,4-dihydro-2H-1,4-benzoxazine (described in J. Heterocyclic Chem., 1985, 22, 177) in 10 ml of ethanol and 10 ml of tetrahydrofuran. The reaction mixture is stirred at room temperature for 1 hour. The solvent is evaporated off, and the resulting residue is taken up in an ethyl acetate/water mixture, at acidic pH, and extracted. The organic phase is dried and concentrated. The residue is then dissolved in 90 ml of tetrahydrofuran and the temperature is reduced to -50° C. before the addition of 45.2 mmol (22.6 ml) of lithium diisopropylamide as a 2M solution in tetrahydrofuran. The reaction mixture is stirred for 2 hours at -50° C., and then 45.2 mmol (2.7 ml) of iodomethane are added and the temperature is brought back up to 25° C. in the course of 2 hours. After hydrolysis, the mixture is acidified to pH=4 and extracted with ethyl acetate. The organic phase is dried and concentrated. The residue is then dissolved in 150 ml of methanol in the presence of para-toluenesulphonic acid. The reaction mixture is heated at reflux for 18 hours. The solvent is evaporated off, and the mixture is taken up in an ethyl acetate/water mixture and extracted. The organic phase is dried, concentrated and purified by chromatography on silica gel using an ethyl acetate/petroleum ether mixture (3/7) as eluant to yield the expected compound. The solvent is evaporated off extracted The organic phase is dried concentrated The residue is then dissolved in 90 ml of tetrahydrofuran The reaction mixture is stirred for 2 hours at -50° C. is brought back up to 25° C. in the course of 2 hours After hydrolysis extracted with ethyl acetate The organic phase is dried concentrated The residue is then dissolved in 150 ml of methanol in the presence of para-toluenesulphonic acid The reaction mixture is heated at reflux for 18 hours The solvent is evaporated off extracted The organic phase is dried concentrated purified by chromatography on silica gel using an ethyl acetate/petroleum ether mixture (3/7) as eluant

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a sealable vessel, potassium carbonate (56 mg, 0.41 mmol) was added to a solution of (±)-ethyl 3,4-dihydro-2H-benzo[b][1,4]oxazine-2-carboxylate (60 mg, 0.29 mmol) and iodomethane (22 □L, 0.35 mmol) in acetone (2 mL). The vessel was sealed and the reaction mixture was stirred at 60° C. for 24 h. The mixture was cooled to ambient temperature, diluted with dichloromethane (60 mL), and the organic layer was extracted with water (10 mL) and half-saturated brine (10 mL). The organic layer was dried over sodium sulfate and concentrated. Purification of the concentrate by flash column chromatography (5% to 10% EtOAc/hexane) afforded the title compound (43 mg, 0.19 mmol). MS m/z: 222 (M+1). The vessel was sealed The mixture was cooled to ambient temperature the organic layer was extracted with water (10 mL) and half-saturated brine (10 mL) The organic layer was dried over sodium sulfate concentrated Purification of the concentrate by flash column chromatography (5% to 10% EtOAc/hexane)