methyl 2-chloro-4-iodobenzoate

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

実験手順: Following the basic procedure of Example 11(d), by reacting 1.2 g (5 mmol) of α-ethynyl-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenemethanol with 1.6 g (5 mmol) of methyl 2-chloro-4-iodobenzoate, 1.7 g (83%) of the expected ester was obtained in the form of a brown oil.

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

実験手順: Following the basic procedure of Example 11(d), by reacting 1.2 g (5 mmol) of α-ethynyl-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenemethanol with 1.6 g (5 mmol) of methyl 2-chloro-4-iodobenzoate, 1.7 g (83%) of the expected ester was obtained in the form of a brown oil.

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

実験手順: Following the basic procedure of Example 11(d), by reacting 1.2 g (5 mmol) of α-ethynyl-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenemethanol with 1.6 g (5 mmol) of methyl 2-chloro-4-iodobenzoate, 1.7 g (83%) of the expected ester was obtained in the form of a brown oil.

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

実験手順: To methyl 2-chloro-4-iodobenzoate (296 mg) was added a solution (4.5 mL) of 2-tert-butoxy-2-oxoethylzinc bromide in THF, then, bis(tri-tert-butylphosphine)palladium (51 mg) was added, and a reaction was performed at 50 W and 80° C. for 10 minutes using a microwave synthesis apparatus manufactured by CEM Co. The reaction solution was poured into an aqueous saturated ammonium chloride solution, and ethyl acetate was added. Insolubles were filtered off with Celite, and layers were separated. The organic layer was washed with an aqueous saturated sodium chloride solution, dried with anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by medium pressure preparative liquid chromatography W-prep 2XY (column: main column M, inject column S; automatic condition setting: n-hexane:ethyl acetate=4:1, Rf=0.60) to obtain the title compound (94 mg) having following physical property values. a microwave synthesis apparatus was added Insolubles were filtered off with Celite, and layers were separated The organic layer was washed with an aqueous saturated sodium chloride solution dried with anhydrous sodium sulfate concentrated under reduced pressure The resulting residue was purified by medium pressure preparative liquid chromatography W-prep 2XY (column: main column M, inject column S; automatic condition setting: n-hexane:ethyl acetate=4:1, Rf=0.60)

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

実験手順: 4-Amino-2-methoxy-benzoic acid methyl ester (22.97 g) was cooled to an internal temperature of −10° C. in concentrated hydrochloric acid (110 ml) and stirred as a suspension. A precooled solution of sodium nitrite (98.71 g) in water (45 ml) was added to this mixture, at such a rate so as to maintain a reaction temperature of less than 0° C. After stirring for 25 minutes at 0° C. the reaction was treated with a solution of potassium iodide (24.44 g) and iodine (18.37 g) in water (50 ml) at such a rate so as to maintain a reaction temperature of less than −4° C. Ethyl acetate (100 ml) was added during the addition and the dark mixture was stirred at 0° C. for one hour. The organic layer was diluted with ethyl acetate and washed well with saturated sodium thiosulfate solution. The resulting orange solution was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated in vacuo to yield an oil which was purified by suction filtration through silica gel eluting with hexane/ethyl acetate (50/1). The resulting purified oil solidified on cooling to give 33.71 g of the title compound. MS, m/z: 296 (M)+. at such a rate so as to maintain a reaction temperature of less than 0° C After stirring for 25 minutes at 0° C. the reaction to maintain a reaction temperature of less than −4° C the dark mixture was stirred at 0° C. for one hour washed well with saturated sodium thiosulfate solution The resulting orange solution was washed with brine dried over anhydrous magnesium sulfate The solvent was evaporated in vacuo to yield an oil which was purified by suction filtration through silica gel eluting with hexane/ethyl acetate (50/1) The resulting purified oil on cooling

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

実験手順: To methyl 2-chloro-4-iodobenzoate (296 mg) was added a solution (4.5 mL) of 2-tert-butoxy-2-oxoethylzinc bromide in THF, then, bis(tri-tert-butylphosphine)palladium (51 mg) was added, and a reaction was performed at 50 W and 80° C. for 10 minutes using a microwave synthesis apparatus manufactured by CEM Co. The reaction solution was poured into an aqueous saturated ammonium chloride solution, and ethyl acetate was added. Insolubles were filtered off with Celite, and layers were separated. The organic layer was washed with an aqueous saturated sodium chloride solution, dried with anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by medium pressure preparative liquid chromatography W-prep 2XY (column:main column M, inject column S; automatic condition setting: n-hexane:ethyl acetate=4:1, Rf=0.60) to obtain the title compound (94 mg) having following physical property values. a microwave synthesis apparatus was added Insolubles were filtered off with Celite, and layers were separated The organic layer was washed with an aqueous saturated sodium chloride solution dried with anhydrous sodium sulfate concentrated under reduced pressure The resulting residue was purified by medium pressure preparative liquid chromatography W-prep 2XY (column:main column M, inject column S; automatic condition setting: n-hexane:ethyl acetate=4:1, Rf=0.60)

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

実験手順: Following the basic procedure of Example 11(d), by reacting 1.2 g (5 mmol) of α-ethynyl-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenemethanol with 1.6 g (5 mmol) of methyl 2-chloro-4-iodobenzoate, 1.7 g (83%) of the expected ester was obtained in the form of a brown oil.

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

実験手順: Following the basic procedure of Example 11(d), by reacting 1.2 g (5 mmol) of α-ethynyl-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenemethanol with 1.6 g (5 mmol) of methyl 2-chloro-4-iodobenzoate, 1.7 g (83%) of the expected ester was obtained in the form of a brown oil.

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

実験手順: 4-Amino-2-methoxy-benzoic acid methyl ester (22.97 g) was cooled to an internal temperature of −10° C. in concentrated hydrochloric acid (110 ml) and stirred as a suspension. A precooled solution of sodium nitrite (98.71 g) in water (45 ml) was added to this mixture, at such a rate so as to maintain a reaction temperature of less than 0° C. After stirring for 25 minutes at 0° C. the reaction was treated with a solution of potassium iodide (24.44 g) and iodine (18.37 g) in water (50 ml) at such a rate so as to maintain a reaction temperature of less than −40° C. Ethyl acetate (100 ml) was added during the addition and the dark mixture was stirred at 0° C. for one hour. The organic layer was diluted with ethyl acetate and washed well with saturated sodium thiosulfate solution. The resulting orange solution was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated in vacuo to yield an oil which was purified by suction filtration through silica gel eluting with hexane/ethyl acetate (50/1). The resulting purified oil solidified on cooling to give 33.71 g of the title compound. MS, m/z: 296 (M)+. at such a rate so as to maintain a reaction temperature of less than 0° C After stirring for 25 minutes at 0° C. the reaction to maintain a reaction temperature of less than −40° C the dark mixture was stirred at 0° C. for one hour washed well with saturated sodium thiosulfate solution The resulting orange solution was washed with brine dried over anhydrous magnesium sulfate The solvent was evaporated in vacuo to yield an oil which was purified by suction filtration through silica gel eluting with hexane/ethyl acetate (50/1) The resulting purified oil on cooling

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

実験手順: 4-Amino-2-methoxy-benzoic acid methyl ester (22.97 g) was cooled to an internal temperature of −10° C. in concentrated hydrochloric acid (110 ml) and stirred as a suspension. A precooled solution of sodium nitrite (98.71 g) in water (45 ml) was added to this mixture, at such a rate so as to maintain a reaction temperature of less than 0° C. After stirring for 25 minutes at 0° C. the reaction was treated with a solution of potassium iodide (24.44 g) and iodine (18.37 g) in water (50 ml) at such a rate so as to maintain a reaction temperature of less than −40° C. Ethyl acetate (100 ml) was added during the addition and the dark mixture was stirred at 0° C. for one hour. The organic layer was diluted with ethyl acetate and washed well with saturated sodium thiosulfate solution. The resulting orange solution was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated in vacuo to yield an oil which was purified by suction filtration through silica gel eluting with hexane/ethyl acetate (50/1). The resulting purified oil solidified on cooling to give 33.71 g of the title compound. MS, m/z: 296 (M)+. at such a rate so as to maintain a reaction temperature of less than 0° C After stirring for 25 minutes at 0° C. the reaction to maintain a reaction temperature of less than −40° C the dark mixture was stirred at 0° C. for one hour washed well with saturated sodium thiosulfate solution The resulting orange solution was washed with brine dried over anhydrous magnesium sulfate The solvent was evaporated in vacuo to yield an oil which was purified by suction filtration through silica gel eluting with hexane/ethyl acetate (50/1) The resulting purified oil on cooling

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

実験手順: To methyl 2-chloro-4-iodobenzoate (296 mg) was added a solution (4.5 mL) of 2-tert-butoxy-2-oxoethylzinc bromide in THF, then, bis(tri-tert-butylphosphine)palladium (51 mg) was added, and a reaction was performed at 50 W and 80° C. for 10 minutes using a microwave synthesis apparatus manufactured by CEM Co. The reaction solution was poured into an aqueous saturated ammonium chloride solution, and ethyl acetate was added. Insolubles were filtered off with Celite, and layers were separated. The organic layer was washed with an aqueous saturated sodium chloride solution, dried with anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by medium pressure preparative liquid chromatography W-prep 2XY (column: main column M, inject column S; automatic condition setting: n-hexane:ethyl acetate=4:1, Rf=0.60) to obtain the title compound (94 mg) having following physical property values. a microwave synthesis apparatus was added Insolubles were filtered off with Celite, and layers were separated The organic layer was washed with an aqueous saturated sodium chloride solution dried with anhydrous sodium sulfate concentrated under reduced pressure The resulting residue was purified by medium pressure preparative liquid chromatography W-prep 2XY (column: main column M, inject column S; automatic condition setting: n-hexane:ethyl acetate=4:1, Rf=0.60)