1-[4-(morpholin-4-ylmethyl)phenyl]ethanone

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:125.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a 20 ml microwave vial, 5-fluoroisatin (650 mg, 4 mmol) was suspended in ethanol (7 ml), then, 1-[4-(morpholinomethyl)phenyl]ethanone (preparation 6) (863 mg, 4 mmol) was added followed by water (7 ml). To this suspension potassium hydroxide (2.21 g, 39 mmol) was added at room temperature. The microwave vial was sealed and the reaction mixture was heated at 125° C. for 20 min under microwave irradiation. The resulting solution was diluted with water (50 ml) and adjusted to pH 7-8 with 10% HCl. The resulting precipitate was filtered and washed with water (50 ml) and ethyl acetate (100 ml) to obtain the desired product as an off-white solid (1.1 g, Yield: 76%). The microwave vial was sealed The resulting precipitate was filtered washed with water (50 ml) and ethyl acetate (100 ml)

反応条件: temp:125.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a 20 ml microwave vial, 5-fluoroisatin (650 mg, 4 mmol) was suspended in ethanol (7 ml), then, 1-[4-(morpholinomethyl)phenyl]ethanone (preparation 6) (863 mg, 4 mmol) was added followed by water (7 ml). To this suspension potassium hydroxide (2.21 g, 39 mmol) was added at room temperature. The microwave vial was sealed and the reaction mixture was heated at 125° C. for 20 min under microwave irradiation. The resulting solution was diluted with water (50 ml) and adjusted to pH 7-8 with 10% HCl. The resulting precipitate was filtered and washed with water (50 ml) and ethyl acetate (100 ml) to obtain the desired product as an off-white solid (1.1 g, Yield: 76%). The microwave vial was sealed The resulting precipitate was filtered washed with water (50 ml) and ethyl acetate (100 ml)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred suspension of 4-(morpholinomethyl)benzonitrile (preparation 5) (1.00 g, 5 mmol) in toluene (19 ml), 3M methyl magnesium bromide in ethyl ether (5 ml, 15 mmol) was added at room temperature under argon. The resulting suspension was refluxed for 4 h, allowed to reach room temperature and then cooled down to 0° C., acidified with 10% HCl and then heated to reflux for 1 h. The two phases were separated and the aqueous phase rinsed with ethyl acetate, then brought to pH 10 with NH4OH and extracted with DCM. The phases were separated and the organic phase was dried over MgSO4 and concentrated under reduced pressure. The crude product was purified by flash column chromatography using an 80 g silica gel cartridge and eluting with DCM (Solvent A) and MeOH (Solvent B) and the following gradient: 1 min hold 100% A followed by a 12 min ramp to 2.5% B and then 5 min hold at 2.5% B. The desired fractions were concentrated to dryness under vacuum to obtain the desired compound as a white solid (0.79 g, 3.6 mmol, Yield: 70%). was added at room temperature under argon The resulting suspension was refluxed for 4 h to reach room temperature heated to reflux for 1 h The two phases were separated the aqueous phase rinsed with ethyl acetate extracted with DCM The phases were separated the organic phase was dried over MgSO4 concentrated under reduced pressure The crude product was purified by flash column chromatography eluting with DCM (Solvent A) and MeOH (Solvent B) 1 min 5 min The desired fractions were concentrated to dryness under vacuum

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

実験手順: 4.7 g of 1,4-dihydro-2,6-dimethyl-3,5-pyridinecarboxylate and 1.3 g of scandium triflate were added to 2.75 g of 4-acetylbenzaldehyde (18.56 mmol), 1.7 ml of morpholine and 3 g of 4 Å molecular sieves in 100 ml of tetrahydrofuran under argon, and the mixture was heated to reflux for 3 hours. The mixture was concentrated. The residue was mixed with ethyl acetate and washed with sat. NaHCO3 solution and sat. NaCl solution. Drying and evaporation of the mixture resulted in a crude product which was purified by chromatography on silica gel (eluent: cyclohexane/ethyl acetate 40-80%). 1.85 g of a yellowish oil were obtained. the mixture was heated to reflux for 3 hours The mixture was concentrated The residue was mixed with ethyl acetate washed with sat. NaHCO3 solution and sat. NaCl solution Drying evaporation of the mixture resulted in a crude product which was purified by chromatography on silica gel (eluent: cyclohexane/ethyl acetate 40-80%)

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

実験手順: 4.7 g of 1,4-dihydro-2,6-dimethyl-3,5-pyridinecarboxylate and 1.3 g of scandium triflate were added to 2.75 g of 4-acetylbenzaldehyde (18.56 mmol), 1.7 ml of morpholine and 3 g of 4 Å molecular sieves in 100 ml of tetrahydrofuran under argon, and the mixture was heated to reflux for 3 hours. The mixture was concentrated. The residue was mixed with ethyl acetate and washed with sat. NaHCO3 solution and sat. NaCl solution. Drying and evaporation of the mixture resulted in a crude product which was purified by chromatography on silica gel (eluent: cyclohexane/ethyl acetate 40-80%). 1.85 g of a yellowish oil were obtained. the mixture was heated to reflux for 3 hours The mixture was concentrated The residue was mixed with ethyl acetate washed with sat. NaHCO3 solution and sat. NaCl solution Drying evaporation of the mixture resulted in a crude product which was purified by chromatography on silica gel (eluent: cyclohexane/ethyl acetate 40-80%)

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

実験手順: 4.7 g of 1,4-dihydro-2,6-dimethyl-3,5-pyridinecarboxylate and 1.3 g of scandium triflate were added to 2.75 g of 4-acetylbenzaldehyde (18.56 mmol), 1.7 ml of morpholine and 3 g of 4 Å molecular sieves in 100 ml of tetrahydrofuran under argon, and the mixture was heated to reflux for 3 hours. The mixture was concentrated. The residue was mixed with ethyl acetate and washed with sat. NaHCO3 solution and sat. NaCl solution. Drying and evaporation of the mixture resulted in a crude product which was purified by chromatography on silica gel (eluent: cyclohexane/ethyl acetate 40-80%). 1.85 g of a yellowish oil were obtained. the mixture was heated to reflux for 3 hours The mixture was concentrated The residue was mixed with ethyl acetate washed with sat. NaHCO3 solution and sat. NaCl solution Drying evaporation of the mixture resulted in a crude product which was purified by chromatography on silica gel (eluent: cyclohexane/ethyl acetate 40-80%)

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

実験手順: 4.7 g of 1,4-dihydro-2,6-dimethyl-3,5-pyridinecarboxylate and 1.3 g of scandium triflate were added to 2.75 g of 4-acetylbenzaldehyde (18.56 mmol), 1.7 ml of morpholine and 3 g of 4 Å molecular sieves in 100 ml of tetrahydrofuran under argon, and the mixture was heated to reflux for 3 hours. The mixture was concentrated. The residue was mixed with ethyl acetate and washed with sat. NaHCO3 solution and sat. NaCl solution. Drying and evaporation of the mixture resulted in a crude product which was purified by chromatography on silica gel (eluent: cyclohexane/ethyl acetate 40-80%). 1.85 g of a yellowish oil were obtained. the mixture was heated to reflux for 3 hours The mixture was concentrated The residue was mixed with ethyl acetate washed with sat. NaHCO3 solution and sat. NaCl solution Drying evaporation of the mixture resulted in a crude product which was purified by chromatography on silica gel (eluent: cyclohexane/ethyl acetate 40-80%)

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

実験手順: 4.7 g of 1,4-dihydro-2,6-dimethyl-3,5-pyridinecarboxylate and 1.3 g of scandium triflate were added to 2.75 g of 4-acetylbenzaldehyde (18.56 mmol), 1.7 ml of morpholine and 3 g of 4 Å molecular sieves in 100 ml of tetrahydrofuran under argon, and the mixture was heated to reflux for 3 hours. The mixture was concentrated. The residue was mixed with ethyl acetate and washed with sat. NaHCO3 solution and sat. NaCl solution. Drying and evaporation of the mixture resulted in a crude product which was purified by chromatography on silica gel (eluent: cyclohexane/ethyl acetate 40-80%). 1.85 g of a yellowish oil were obtained. the mixture was heated to reflux for 3 hours The mixture was concentrated The residue was mixed with ethyl acetate washed with sat. NaHCO3 solution and sat. NaCl solution Drying evaporation of the mixture resulted in a crude product which was purified by chromatography on silica gel (eluent: cyclohexane/ethyl acetate 40-80%)

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

実験手順: 4.7 g of 1,4-dihydro-2,6-dimethyl-3,5-pyridinecarboxylate and 1.3 g of scandium triflate were added to 2.75 g of 4-acetylbenzaldehyde (18.56 mmol), 1.7 ml of morpholine and 3 g of 4 Å molecular sieves in 100 ml of tetrahydrofuran under argon, and the mixture was heated to reflux for 3 hours. The mixture was concentrated. The residue was mixed with ethyl acetate and washed with sat. NaHCO3 solution and sat. NaCl solution. Drying and evaporation of the mixture resulted in a crude product which was purified by chromatography on silica gel (eluent: cyclohexane/ethyl acetate 40-80%). 1.85 g of a yellowish oil were obtained. the mixture was heated to reflux for 3 hours The mixture was concentrated The residue was mixed with ethyl acetate washed with sat. NaHCO3 solution and sat. NaCl solution Drying evaporation of the mixture resulted in a crude product which was purified by chromatography on silica gel (eluent: cyclohexane/ethyl acetate 40-80%)

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

実験手順: 4.7 g of 1,4-dihydro-2,6-dimethyl-3,5-pyridinecarboxylate and 1.3 g of scandium triflate were added to 2.75 g of 4-acetylbenzaldehyde (18.56 mmol), 1.7 ml of morpholine and 3 g of 4 Å molecular sieves in 100 ml of tetrahydrofuran under argon, and the mixture was heated to reflux for 3 hours. The mixture was concentrated. The residue was mixed with ethyl acetate and washed with sat. NaHCO3 solution and sat. NaCl solution. Drying and evaporation of the mixture resulted in a crude product which was purified by chromatography on silica gel (eluent: cyclohexane/ethyl acetate 40-80%). 1.85 g of a yellowish oil were obtained. the mixture was heated to reflux for 3 hours The mixture was concentrated The residue was mixed with ethyl acetate washed with sat. NaHCO3 solution and sat. NaCl solution Drying evaporation of the mixture resulted in a crude product which was purified by chromatography on silica gel (eluent: cyclohexane/ethyl acetate 40-80%)

反応条件: temp:125.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a 20 ml microwave vial, 5-fluoroisatin (650 mg, 4 mmol) was suspended in ethanol (7 ml), then, 1-[4-(morpholinomethyl)phenyl]ethanone (preparation 6) (863 mg, 4 mmol) was added followed by water (7 ml). To this suspension potassium hydroxide (2.21 g, 39 mmol) was added at room temperature. The microwave vial was sealed and the reaction mixture was heated at 125° C. for 20 min under microwave irradiation. The resulting solution was diluted with water (50 ml) and adjusted to pH 7-8 with 10% HCl. The resulting precipitate was filtered and washed with water (50 ml) and ethyl acetate (100 ml) to obtain the desired product as an off-white solid (1.1 g, Yield: 76%). The microwave vial was sealed The resulting precipitate was filtered washed with water (50 ml) and ethyl acetate (100 ml)