propyl methanesulfonate

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into 2 ml of DMF were dissolved 200 mg (0.68 mmol) of cis-3-amino-4-methyl-1-(1-methylindazol-3-ylcarbonyl)pyrrolidine hydrochloride and 0.11 ml (0.81 mmol) of triethylamine, and 188 mg (1.36 mmol) of n-propyl methanesulfonate was added under ice cooling. Then, the mixture was stirred for 5 hours at room temperature, for 3 hours at 60° C. and further for 5 hours at 70° C. After addition of water, the solution was made alkaline with sodium bicarbonate, which was then extracted with methylene chloride. After washed with saturated saline solution and dried over anhydrous magnesium sulfate, the solution was concentrated under reduced pressure to obtain crude oil. This was subjected to silica gel column chromatographic purification (methylene chloride:methanol=20:1) to obtain 57 mg (27.9%) of aimed compound (pale yellow oil). was added under ice cooling was then extracted with methylene chloride After washed with saturated saline solution dried over anhydrous magnesium sulfate the solution was concentrated under reduced pressure to obtain crude oil This was subjected to silica gel column chromatographic purification (methylene chloride:methanol=20:1)

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into 2 ml of DMF were dissolved 200 mg (0.68 mmol) of cis-3-amino-4-methyl-1-(1-methylindazol-3-ylcarbonyl)pyrrolidine hydrochloride and 0.11 ml (0.81 mmol) of triethylamine, and 188 mg (1.36 mmol) of n-propyl methanesulfonate was added under ice cooling. Then, the mixture was stirred for 5 hours at room temperature, for 3 hours at 60° C. and further for 5 hours at 70° C. After addition of water, the solution was made alkaline with sodium bicarbonate, which was then extracted with methylene chloride. After washed with saturated saline solution and dried over anhydrous magnesium sulfate, the solution was concentrated under reduced pressure to obtain crude oil. This was subjected to silica gel column chromatographic purification (methylene chloride:methanol=20:1) to obtain 57 mg (27.9%) of aimed compound (pale yellow oil). was added under ice cooling was then extracted with methylene chloride After washed with saturated saline solution dried over anhydrous magnesium sulfate the solution was concentrated under reduced pressure to obtain crude oil This was subjected to silica gel column chromatographic purification (methylene chloride:methanol=20:1)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 50 ml four necked flask equipped with a stirrer, a dropping funnel, a cooling tube and a thermometer, 41.05 g (0.5 mol) of 1-methyl imidazole and 50 ml of toluene were charged and, after heating at 80° C., 76.00 g (0.55 mol) of propyl methane sulfonate was dropped slowly taking one hour or more. They were stirred at a refluxing temperature for 40 hours. After cooling, solvent cleaning was conducted with toluene to obtain 99.13 g of 1-methyl-3-propyl-imidazolium methane sulfonate salt by drying under a reduced pressure. Then, 99.13 g of the obtained 1-ethyl-3-propyl imidazolium.methane sulfonate salt was dissolved in 80 ml of water, and a solution in which 139.24 g of lithium bis(trifluoromethane sulfonyl) imide was dissolved in 80 ml of water was added thereto at a room temperature and stirred. From separated two layers, the lower layer was fractionated and by-products were removed by adding 40 wt % of purified water and by water washing five times, and vacuum drying was applied to obtain 178.75 g of 1-methyl-3-propyl imidazolium bis(trifluoromethane sulfonyl) imide. As a result of ICP analysis, the total alkali metal was 2.1 ppm or less, the chloride ion was 0.6 ppm and each of iodide and bromide ions was 0.1 ppm or less (less than ICP detection limit). taking one hour or more After cooling

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Methyl 7-hydroxy-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxylate (394 mg), propoxyphenyl)propyl methanesulfonate (1099 mg) and potassium carbonate (304 mg) were suspended in DMF (15 ml), and the resulting suspension was stirred at 70° C. for 5 hours. The reaction mixture was diluted with ethyl acetate and was washed respectively with water and an aqueous saturated solution of sodium chloride, and the organic layer was dried with anhydrous magnesium sulfate. After concentration under reduced pressure to remove the solvent, is the residue was purified by silica gel column chromatography (hexane:ethyl acetate=3:1) to obtain methyl 7-[3-(3-propoxyphenyl)propoxy]-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxylate (765 mg) as a yellow oil. was washed respectively with water an aqueous saturated solution of sodium chloride, and the organic layer was dried with anhydrous magnesium sulfate After concentration under reduced pressure to remove the solvent was purified by silica gel column chromatography (hexane:ethyl acetate=3:1)