methyl 3-(chloromethyl)benzoate

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 94 mg (0.23 mmol) of 2-methyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-2,3-dihydro-1H-indole in 0.5 mL of DMF were added 104 mg (0.45 mmol) of 3-chloromethyl-benzoic acid methyl ester and the mixture was stirred at 80° C. for 10 hrs. After cooling to RT the mixture was treated with 0.5 mL of a 1M solution of TBAF in THF and stirred for an hour at 60° C. Evaporation of the solvent and chromatography on silica gel with EtOAc/n-heptane gave 58 mg (99%) of 3-[2-methyl-5-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-ylmethyl]-benzoic acid methyl ester, light red oil, MS: 448 (MH+). After cooling to RT the mixture stirred for an hour at 60° C Evaporation of the solvent and chromatography on silica gel with EtOAc/n-heptane

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

実験手順: To a solution of phenothiazine (1.00 g) in tetrahydrofuran (10 ml) was added potassium tert-butoxide (617 mg) at 0° C. The mixture was stirred at 0° C. for 20 minutes, and then a solution of methyl 3-(chloromethyl)benzoate (1.02 g) in tetrahydrofuran (10 ml) was added. The mixture was stirred at 25° C. for 3 hours, and then potassium tert-butoxide (1.02 g) was added. The mixture was stirred at 25° C. for 1 hour, and then evaporated. The residue was partitioned between ethyl acetate and 0.1N hydrochloric acid. The organic layer was washed with water and brine, dried over magnesium sulfate, and evaporated. The residue was chromatographed on silica gel eluting with a mixture of hexane and ethyl acetate (40:1) to give tert-butyl 3-(phenothiazin-10-ylmethyl)benzoate (598 mg) as crystals. The mixture was stirred at 25° C. for 3 hours The mixture was stirred at 25° C. for 1 hour evaporated The residue was partitioned between ethyl acetate and 0.1N hydrochloric acid The organic layer was washed with water and brine dried over magnesium sulfate evaporated The residue was chromatographed on silica gel eluting with a mixture of hexane and ethyl acetate (40:1)

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

実験手順: To a solution of phenothiazine (1.00 g) in tetrahydrofuran (10 ml) was added potassium tert-butoxide (617 mg) at 0° C. The mixture was stirred at 0° C. for 20 minutes, and then a solution of methyl 3-(chloromethyl)benzoate (1.02 g) in tetrahydrofuran (10 ml) was added. The mixture was stirred at 25° C. for 3 hours, and then potassium tert-butoxide (1.02 g) was added. The mixture was stirred at 25° C. for 1 hour, and then evaporated. The residue was partitioned between ethyl acetate and 0.1N hydrochloric acid. The organic layer was washed with water and brine, dried over magnesium sulfate, and evaporated. The residue was chromatographed on silica gel eluting with a mixture of hexane and ethyl acetate (40:1) to give tert-butyl 3-(phenothiazin-10-ylmethyl)benzoate (598 mg) as crystals. The mixture was stirred at 25° C. for 3 hours The mixture was stirred at 25° C. for 1 hour evaporated The residue was partitioned between ethyl acetate and 0.1N hydrochloric acid The organic layer was washed with water and brine dried over magnesium sulfate evaporated The residue was chromatographed on silica gel eluting with a mixture of hexane and ethyl acetate (40:1)

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

実験手順: To a solution of phenoxazine (2.20 g) in tetrahydrofuran (30 ml) was added potassium tert-butoxide (2.69 g) at 0° C. The mixture was stirred at 0° C. for 10 minutes, and then a solution of methyl 3-(chloromethyl)benzoate (2.44 g) in tetrahydrofuran (20 ml) was added. The mixture was stirred at 25° C. for 30 minutes, and then evaporated. The residue was partitioned between ethyl acetate and 0.1N hydrochloric acid. The organic layer was washed with water and brine, dried over magnesium sulfate, and evaporated. The residue was purified by chromatography on silica gel eluting with a mixture of hexane and ethyl acetate (40:1-20:1) and recrystallization from a mixture of hexane and ethyl acetate to give e methyl 3-(phenoxazin-10-ylmethyl)benzoate (1.12 g) as crystals. The mixture was stirred at 25° C. for 30 minutes evaporated The residue was partitioned between ethyl acetate and 0.1N hydrochloric acid The organic layer was washed with water and brine dried over magnesium sulfate evaporated The residue was purified by chromatography on silica gel eluting with a mixture of hexane and ethyl acetate (40:1-20:1) and recrystallization from a mixture of hexane and ethyl acetate

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

実験手順: To a solution of phenoxazine (2.20 g) in tetrahydrofuran (30 ml) was added potassium tert-butoxide (2.69 g) at 0° C. The mixture was stirred at 0° C. for 10 minutes, and then a solution of methyl 3-(chloromethyl)benzoate (2.44 g) in tetrahydrofuran (20 ml) was added. The mixture was stirred at 25° C. for 30 minutes, and then evaporated. The residue was partitioned between ethyl acetate and 0.1N hydrochloric acid. The organic layer was washed with water and brine, dried over magnesium sulfate, and evaporated. The residue was purified by chromatography on silica gel eluting with a mixture of hexane and ethyl acetate (40:1-20:1) and recrystallization from a mixture of hexane and ethyl acetate to give e methyl 3-(phenoxazin-10-ylmethyl)benzoate (1.12 g) as crystals. The mixture was stirred at 25° C. for 30 minutes evaporated The residue was partitioned between ethyl acetate and 0.1N hydrochloric acid The organic layer was washed with water and brine dried over magnesium sulfate evaporated The residue was purified by chromatography on silica gel eluting with a mixture of hexane and ethyl acetate (40:1-20:1) and recrystallization from a mixture of hexane and ethyl acetate

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

実験手順: To a solution of 10,11-dihydro-5H-dibenz[b,f]azepine (2.44 g) in tetrahydrofuran (25 ml) was added potassium tert-butoxide (2.02 g) at 0° C. The mixture was stirred at 0° C. for 15 minutes, and then a solution of methyl 3-(chloromethyl)benzoate (3.57 g) in tetrahydrofuran (15 ml) was added. The mixture was stirred at 25° C. for 1 hour, and then evaporated. The residue was partitioned between ethyl acetate and 0.1N hydrochloric acid. The organic layer was washed with water and brine, dried over magnesium sulfate, and evaporated. The residue was chromatographed on silica gel eluting with a mixture of hexane and ethyl acetate (40:1) to give methyl 3-(10,11-dihydro-5H-dibenz[b,f]azepin-5-ylmethyl)benzoate (1.10 g) as an oil. The mixture was stirred at 25° C. for 1 hour evaporated The residue was partitioned between ethyl acetate and 0.1N hydrochloric acid The organic layer was washed with water and brine dried over magnesium sulfate evaporated The residue was chromatographed on silica gel eluting with a mixture of hexane and ethyl acetate (40:1)

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

実験手順: To a solution of 10,11-dihydro-5H-dibenz[b,f]azepine (2.44 g) in tetrahydrofuran (25 ml) was added potassium tert-butoxide (2.02 g) at 0° C. The mixture was stirred at 0° C. for 15 minutes, and then a solution of methyl 3-(chloromethyl)benzoate (3.57 g) in tetrahydrofuran (15 ml) was added. The mixture was stirred at 25° C. for 1 hour, and then evaporated. The residue was partitioned between ethyl acetate and 0.1N hydrochloric acid. The organic layer was washed with water and brine, dried over magnesium sulfate, and evaporated. The residue was chromatographed on silica gel eluting with a mixture of hexane and ethyl acetate (40:1) to give methyl 3-(10,11-dihydro-5H-dibenz[b,f]azepin-5-ylmethyl)benzoate (1.10 g) as an oil. The mixture was stirred at 25° C. for 1 hour evaporated The residue was partitioned between ethyl acetate and 0.1N hydrochloric acid The organic layer was washed with water and brine dried over magnesium sulfate evaporated The residue was chromatographed on silica gel eluting with a mixture of hexane and ethyl acetate (40:1)

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

実験手順: To a solution of phenothiazine (1.00 g) in tetrahydrofuran (10 ml) was added potassium tert-butoxide (617 mg) at 0° C. The mixture was stirred at 0° C. for 20 minutes, and then a solution of methyl 3-(chloromethyl)benzoate (1.02 g) in tetrahydrofuran (10 ml) was added. The mixture was stirred at 25° C. for 3 hours, and then potassium tert-butoxide (1.02 g) was added. The mixture was stirred at 25° C. for 1 hour, and then evaporated. The residue was partitioned between ethyl acetate and 0.1N hydrochloric acid. The organic layer was washed with water and brine, dried over magnesium sulfate, and evaporated. The residue was chromatographed on silica gel eluting with a mixture of .hexane and ethyl acetate (40:1) to give tert-butyl 3-(phenothiazin-10-ylmethyl)benzoate (598 mg) as crystals. The mixture was stirred at 25° C. for 3 hours The mixture was stirred at 25° C. for 1 hour evaporated The residue was partitioned between ethyl acetate and 0.1N hydrochloric acid The organic layer was washed with water and brine dried over magnesium sulfate evaporated The residue was chromatographed on silica gel eluting with a mixture of

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

実験手順: To a solution of phenothiazine (1.00 g) in tetrahydrofuran (10 ml) was added potassium tert-butoxide (617 mg) at 0° C. The mixture was stirred at 0° C. for 20 minutes, and then a solution of methyl 3-(chloromethyl)benzoate (1.02 g) in tetrahydrofuran (10 ml) was added. The mixture was stirred at 25° C. for 3 hours, and then potassium tert-butoxide (1.02 g) was added. The mixture was stirred at 25° C. for 1 hour, and then evaporated. The residue was partitioned between ethyl acetate and 0.1N hydrochloric acid. The organic layer was washed with water and brine, dried over magnesium sulfate, and evaporated. The residue was chromatographed on silica gel eluting with a mixture of .hexane and ethyl acetate (40:1) to give tert-butyl 3-(phenothiazin-10-ylmethyl)benzoate (598 mg) as crystals. The mixture was stirred at 25° C. for 3 hours The mixture was stirred at 25° C. for 1 hour evaporated The residue was partitioned between ethyl acetate and 0.1N hydrochloric acid The organic layer was washed with water and brine dried over magnesium sulfate evaporated The residue was chromatographed on silica gel eluting with a mixture of

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

実験手順: To a solution of phenoxazine (2.20 g) in tetrahydrofuran (30 ml) was added potassium tert-butoxide (2.69 g) at 0° C. The mixture was stirred at 0° C. for 10 minutes, and then a solution of methyl 3-(chloromethyl)benzoate (2.44 g) in tetrahydrofuran (20 ml) was added. The mixture was stirred at 25° C. for 30 minutes, and then evaporated. The residue was partitioned between ethyl acetate and 0.1N hydrochloric acid. The organic layer was washed with water and brine, dried over magnesium sulfate, and evaporated. The residue was purified by chromatography on silica gel eluting with a mixture of hexane and ethyl acetate (40:1-20:1) and recrystallization from a mixture of hexane and ethyl acetate to give e methyl 3-(phenoxazin-10-ylmethyl)benzoate (1.12 g) as crystals. The mixture was stirred at 25° C. for 30 minutes evaporated The residue was partitioned between ethyl acetate and 0.1N hydrochloric acid The organic layer was washed with water and brine dried over magnesium sulfate evaporated The residue was purified by chromatography on silica gel eluting with a mixture of hexane and ethyl acetate (40:1-20:1) and recrystallization from a mixture of hexane and ethyl acetate

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

実験手順: To a solution of 10,11-dihydro-5H-dibenz[b,f]azepine (2.44 g) in tetrahydrofuran (25 ml) was added potassium tert-butoxide (2.02 g) at 0° C. The mixture was stirred at 0° C. for 15 minutes, and then a solution of methyl 3-(chloromethyl)benzoate (3.57 g) in tetrahydrofuran (15 ml) was added. The mixture was stirred at 25° C. for 1 hour, and then evaporated. The residue was partitioned between ethyl acetate and 0.1N hydrochloric acid. The organic layer was washed with water and brine, dried over magnesium sulfate, and evaporated. The residue was chromatographed on silica gel eluting with a mixture of hexane and ethyl acetate (40:1) to give methyl 3-(10,11-dihydro-5H-dibenz[b,f]azepin-5-ylmethyl)benzoate (1.10 g) as an oil. The mixture was stirred at 25° C. for 1 hour evaporated The residue was partitioned between ethyl acetate and 0.1N hydrochloric acid The organic layer was washed with water and brine dried over magnesium sulfate evaporated The residue was chromatographed on silica gel eluting with a mixture of hexane and ethyl acetate (40:1)

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

実験手順: To a solution of 10,11-dihydro-5H-dibenz[b,f]azepine (2.44 g) in tetrahydrofuran (25 ml) was added potassium tert-butoxide (2.02 g) at 0° C. The mixture was stirred at 0° C. for 15 minutes, and then a solution of methyl 3-(chloromethyl)benzoate (3.57 g) in tetrahydrofuran (15 ml) was added. The mixture was stirred at 25° C. for 1 hour, and then evaporated. The residue was partitioned between ethyl acetate and 0.1N hydrochloric acid. The organic layer was washed with water and brine, dried over magnesium sulfate, and evaporated. The residue was chromatographed on silica gel eluting with a mixture of hexane and ethyl acetate (40:1) to give methyl 3-(10,11-dihydro-5H-dibenz[b,f]azepin-5-ylmethyl)benzoate (1.10 g) as an oil. The mixture was stirred at 25° C. for 1 hour evaporated The residue was partitioned between ethyl acetate and 0.1N hydrochloric acid The organic layer was washed with water and brine dried over magnesium sulfate evaporated The residue was chromatographed on silica gel eluting with a mixture of hexane and ethyl acetate (40:1)