methyl 3-(hydroxymethyl)-5-iodobenzoate

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

実験手順: The mixture of methyl 5-hydroxymethyl-3-iodobenzoate (5.0 g) and manganese dioxide (30.0 g) in ethyl acetate (50.0 ml) was heated under reflux for 4 hours. The magnganese dioxide was removed by filtration and the filtrate was evaporated in vacuo to give methyl 5-formyl-3-iodobenzoate (2.77 g). was heated under reflux for 4 hours The magnganese dioxide was removed by filtration the filtrate was evaporated in vacuo

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

実験手順: Methanol (20 ml) was added dropwise to a mixture of dimethyl 5-iodoisophthalate (20.0 g) and sodium borohydride (2.4 g) in tetrahydrofuran (200 ml) for 15 minutes at 45-50° C., and the mixture was stirred for 1 hour at same temperature. The reaction mixture was added to a mixture of ethyl acetate and water, and the separated organic layer was washed with brine, dried over magnesium sulfate and evaporated in vacuo. The residue was purified by column chromatography on silica gel with chloroform-methanol (19:1, V/V) as an eluent. The fractions containing the desired product were collected and evaporated in vacuo to give methyl 5-hydroxymethyl-3-iodobenzoate (15.11 g). the separated organic layer was washed with brine dried over magnesium sulfate evaporated in vacuo The residue was purified by column chromatography on silica gel with chloroform-methanol (19:1, V/V) as an eluent The fractions containing the desired product were collected evaporated in vacuo

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

実験手順: To a solution of 3-methoxycarbonyl-5-iodobenzoic acid (1 g) in tetrahydrofuran (10 ml) was added at -40° C. to -30° C. triethylamine (0.55 ml) followed by slow addition of isobutyl chloroformate (0.51 ml) under nitrogen atmosphere. The reaction mixture was stirred below -20° C. for 45 minutes. Then, triethylamine hydrochloride was filtered off and washed with cold tetrahydrofuran, and the filtrate was added as quickly as possible to a suspension of sodium borohydride (0.37 g) in tetrahydrofuran-water (8:1, 8 ml) at 0° C. with vigorous stirring. The stirring was continued at ambient temperature for 4 hours, followed by acidification of the solution to pH 5. The tetrahydrofuran was removed under reduced pressure, and the product was extracted with ethyl acetate. The organic layer was washed with water and brine and dried over magnesium sulfate. Ethyl acetate was removed under reduced pressure and the residue was purified by column chromatography on silica gel eluting with a mixture of chloroform and methanol (30:1). The fractions containing the desired product were collected and evaporated in vacuo to give methyl 3-hydroxymethyl-5-iodobenzoate. Then, triethylamine hydrochloride was filtered off washed with cold tetrahydrofuran the filtrate was added as quickly as possible to a suspension of sodium borohydride (0.37 g) in tetrahydrofuran-water (8:1, 8 ml) at 0° C. with vigorous stirring The stirring was continued at ambient temperature for 4 hours The tetrahydrofuran was removed under reduced pressure the product was extracted with ethyl acetate The organic layer was washed with water and brine dried over magnesium sulfate Ethyl acetate was removed under reduced pressure the residue was purified by column chromatography on silica gel eluting with a mixture of chloroform and methanol (30:1) The fractions containing the desired product were collected evaporated in vacuo

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3.08 g of the 5-hydroxymethyl-3-iodobenzoic acid methyl ester obtained in the production example 2 was dissolved in 50 ml of dry DMF under the flow of nitrogen and then mixed with 2.32 g of the compound in the production example 3, 2.18 g of potassium carbonate and 456 mg of tetrakis(triphenylphosphine) palladium (0). The obtained mixture solution was heated and stirred at 90° C. overnight, mixed with water to stop the reaction, and then extracted with ethyl acetate. The obtained ethyl acetate layer was dried over MgSO4, and the solvent was distilled away. The residue was purified by silica gel column chromatography to obtain 2.05 g (73%) of the title compound. Colorless crystals. The obtained mixture solution was heated the reaction extracted with ethyl acetate The obtained ethyl acetate layer was dried over MgSO4 the solvent was distilled away The residue was purified by silica gel column chromatography