雷诺嗪杂质6

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 26.5 g (0.13 mole) of glycerol guaiacolate in 100 ml of methylene chloride and 10.8 ml (0.13 mole) of pyridine was added in a thin stream to a stirred solution of 17.1 g (0.13 mole) of N-methylsulfamoyl chloride (Preparation 24) in 70 ml of methylene chloride, and the reaction mixture was stirred at ambient temperature for 2 hr. The reaction mixture was treated with 150 ml of water, the layers were separated, and the organic layer was washed successively with a 200 ml portion of 2N hydrochloric acid solution, four 200 ml portions of water, dried (magnesium sulfate), and the solvent was evaporated under reduced pressure to yield a viscous oil. The oil was purified by preparative high pressure liquid chromatography. Fractions containing the desired product were combined and the solvents evaporated under reduced pressure to give 13.9 g (37%) of the title compound as a yellow gum. the layers were separated the organic layer was washed successively with a 200 ml portion of 2N hydrochloric acid solution, four 200 ml portions of water dried (magnesium sulfate) the solvent was evaporated under reduced pressure to yield a viscous oil The oil was purified by preparative high pressure liquid chromatography Fractions containing the desired product the solvents evaporated under reduced pressure

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 3-(2-methoxy-phenoxy)-propane-1,2-diol (4.7 g) in pyridine, cooled at 5°-10° C., is treated under stirring with a solution of p-toluensulphonylchloride (4.5 g) in benzene (70 ml). The reaction mixture is stirred overnight at room temperature, then it is washed with 2N HCl (3×100 ml) and with water, dried on Na2SO4 and evaporated to dryness in vacuum. The oily residue is purified by column chromatography (silica gel 230-400 mesh hexane/AcOEt=3/1) to yield 5 g of 3-(2-methoxy-phenoxy)-2-hydroxy-1-propyl p-toluensulphonate (oil, NMR (--CDCl3):δ=2,4 3H (s) CH3SO2 ; δ=3,75-4,4 5H (m) OCH3 +OCH2. is treated it is washed with 2N HCl (3×100 ml) and with water dried on Na2SO4 evaporated to dryness in vacuum The oily residue is purified by column chromatography (silica gel 230-400 mesh hexane/AcOEt=3/1)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 3-(2-methoxy-phenoxy)-propane-1,2-diol (4.7 g) in pyridine, cooled at 5°-10° C., is treated under stirring with a solution of p-toluensulphonylchloride (4.5 g) in benzene (70 ml). The reaction mixture is stirred overnight at room temperature, then it is washed with 2N HCl (3×100 ml) and with water, dried on Na2SO4 and evaporated to dryness in vacuum. The oily residue is purified by column chromatography (silica gel 230-400 mesh hexane/AcOEt=3/1) to yield 5 g of 3-(2-methoxy-phenoxy)-2-hydroxy-1-propyl p-toluensulphonate (oil, NMR (--CDCl3):δ=2,4 3H (s) CH3SO2 ; δ=3,75-4,4 5H (m) OCH3 +OCH2. is treated it is washed with 2N HCl (3×100 ml) and with water dried on Na2SO4 evaporated to dryness in vacuum The oily residue is purified by column chromatography (silica gel 230-400 mesh hexane/AcOEt=3/1)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The maltitol was similarly admixed with Phase F to form Phase G to which the ammonium glycyrrhizinate was added with another about 5 minutes mixing time being used. The flavors and colorants were then admixed, with a mixing time of about 5 minutes, followed by addition of a sufficient amount of liquid fructose to make the desired volume and mixing to homogeneity. The pH value was thereafter adjusted to be between 4 and 5 using a citric acid or sodium citrate solution. This composition provides 100 mg of guaifenesin per 5 mL (teaspoon). was added with another about 5 minutes mixing time were then admixed, with a mixing time of about 5 minutes mixing to homogeneity

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 26.5 g (0.13 mole) of glycerol guaiacolate in 100 ml of methylene chloride and 10.8 ml (0.13 mole) of pyridine was added in a thin stream to a stirred solution of 17.1 g (0.13 mole) of N-methylsulfamoyl chloride (Preparation 24) in 70 ml of methylene chloride, and the reaction mixture was stirred at ambient temperature for 2 hr. The reaction mixture was treated with 150 ml of water, the layers were separated, and the organic layer was washed successively with a 200 ml portion of 2N hydrochloric acid solution, four 200 ml portions of water, dried (magnesium sulfate), and the solvent was evaporated under reduced pressure to yield a viscous oil. The oil was purified by preparative high pressure liquid chromatography. Fractions containing the desired product were combined and the solvents evaporated under reduced pressure to give 13.9 g (37%) of the title compound as a yellow gum. the layers were separated the organic layer was washed successively with a 200 ml portion of 2N hydrochloric acid solution, four 200 ml portions of water dried (magnesium sulfate) the solvent was evaporated under reduced pressure to yield a viscous oil The oil was purified by preparative high pressure liquid chromatography Fractions containing the desired product the solvents evaporated under reduced pressure

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 26.5 g (0.13 mole) of glycerol guaiacolate in 100 ml of methylene chloride and 10.8 ml (0.13 mole) of pyridine was added in a thin stream to a stirred solution of 17.1 g (0.13 mole) of N-methylsulfamoyl chloride (Preparation 24) in 70 ml of methylene chloride, and the reaction mixture was stirred at ambient temperature for 2 hr. The reaction mixture was treated with 150 ml of water, the layers were separated, and the organic layer was washed successively with a 200 ml portion of 2N hydrochloric acid solution, four 200 ml portions of water, dried (magnesium sulfate), and the solvent was evaporated under reduced pressure to yield a viscous oil. The oil was purified by preparative high pressure liquid chromatography. Fractions containing the desired product were combined and the solvents evaporated under reduced pressure to give 13.9 g (37%) of the title compound as a yellow gum. the layers were separated the organic layer was washed successively with a 200 ml portion of 2N hydrochloric acid solution, four 200 ml portions of water dried (magnesium sulfate) the solvent was evaporated under reduced pressure to yield a viscous oil The oil was purified by preparative high pressure liquid chromatography Fractions containing the desired product the solvents evaporated under reduced pressure

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 3-(2-methoxy-phenoxy)-propane-1,2-diol (4.7 g) in pyridine, cooled at 5°-10° C., is treated under stirring with a solution of p-toluensulphonylchloride (4.5 g) in benzene (70 ml). The reaction mixture is stirred overnight at room temperature, then it is washed with 2N HCl (3×100 ml) and with water, dried on Na2SO4 and evaporated to dryness in vacuum. The oily residue is purified by column chromatography (silica gel 230-400 mesh hexane/AcOEt=3/1) to yield 5 g of 3-(2-methoxy-phenoxy)-2-hydroxy-1-propyl p-toluensulphonate (oil, NMR (--CDCl3):δ=2,4 3H (s) CH3SO2 ; δ=3,75-4,4 5H (m) OCH3 +OCH2. is treated it is washed with 2N HCl (3×100 ml) and with water dried on Na2SO4 evaporated to dryness in vacuum The oily residue is purified by column chromatography (silica gel 230-400 mesh hexane/AcOEt=3/1)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The maltitol was similarly admixed with Phase F to form Phase G to which the ammonium glycyrrhizinate was added with another about 5 minutes mixing time being used. The flavors and colorants were then admixed, with a mixing time of about 5 minutes, followed by addition of a sufficient amount of liquid fructose to make the desired volume and mixing to homogeneity. The pH value was thereafter adjusted to be between 4 and 5 using a citric acid or sodium citrate solution. This composition provides 100 mg of guaifenesin per 5 mL (teaspoon). was added with another about 5 minutes mixing time were then admixed, with a mixing time of about 5 minutes mixing to homogeneity

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 26.5 g (0.13 mole) of glycerol guaiacolate in 100 ml of methylene chloride and 10.8 ml (0.13 mole) of pyridine was added in a thin stream to a stirred solution of 17.1 g (0.13 mole) of N-methylsulfamoyl chloride (Preparation 24) in 70 ml of methylene chloride, and the reaction mixture was stirred at ambient temperature for 2 hr. The reaction mixture was treated with 150 ml of water, the layers were separated, and the organic layer was washed successively with a 200 ml portion of 2N hydrochloric acid solution, four 200 ml portions of water, dried (magnesium sulfate), and the solvent was evaporated under reduced pressure to yield a viscous oil. The oil was purified by preparative high pressure liquid chromatography. Fractions containing the desired product were combined and the solvents evaporated under reduced pressure to give 13.9 g (37%) of the title compound as a yellow gum. the layers were separated the organic layer was washed successively with a 200 ml portion of 2N hydrochloric acid solution, four 200 ml portions of water dried (magnesium sulfate) the solvent was evaporated under reduced pressure to yield a viscous oil The oil was purified by preparative high pressure liquid chromatography Fractions containing the desired product the solvents evaporated under reduced pressure

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 26.5 g (0.13 mole) of glycerol guaiacolate in 100 ml of methylene chloride and 10.8 ml (0.13 mole) of pyridine was added in a thin stream to a stirred solution of 17.1 g (0.13 mole) of N-methylsulfamoyl chloride (Preparation 22) in 70 ml of methylene chloride, and the reaction mixture was stirred at ambient temperature for 2 hr. The reaction mixture was treated with 150 ml of water, the layers were separated, and the organic layer was washed successively with a 200 ml portion of 2N hydrochloric acid solution, four 200 ml portions of water, dried (magnesium sulfate), and the solvent was evaporated under reduced pressure to yield a viscous oil. The oil was purified by preparative high pressure liquid chromatography. Fractions containing the desired product were combined and the solvents evaporated under reduced pressure to give 13.9 g (37%) of the title compound as a yellow gum. the layers were separated the organic layer was washed successively with a 200 ml portion of 2N hydrochloric acid solution, four 200 ml portions of water dried (magnesium sulfate) the solvent was evaporated under reduced pressure to yield a viscous oil The oil was purified by preparative high pressure liquid chromatography Fractions containing the desired product the solvents evaporated under reduced pressure

反应条件: temp:23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 109.3 g (0.55 mole) of glyceryl guaiacolate in 177 ml (2.20 moles) of pyridine and 700 ml methylene chloride was added to a solution of 283 g (2.20 moles) of methylaminosulfonyl chloride in 700 ml of methylene chloride. The addition was made over one hour at 15°-22° C. The solution was stirred at 23° C. for two hours then washed with 3×500 ml water. The methylene chloride solution was dried over type 3A molecular sieves. The mixture was filtered and the filtrate diluted with 140 ml of ethyl acetate. The solution was chromatographed on 2 kg of silica gel using 10% ethyl acetate:methylene chloride solution as eluent. The first 3×750 ml fractions were combined and concentrated to 77.3 g of brown oil. The oil was redissolved in 400 ml of 10% ethyl acetate:methylene chloride solution and chromatographed on 1.5 kg of silica gel. A total of 9×250 ml fractions were collected that showed only one spot on TLC. The addition then washed with 3×500 ml water The methylene chloride solution was dried over type 3A molecular sieves The mixture was filtered the filtrate diluted with 140 ml of ethyl acetate The solution was chromatographed on 2 kg of silica gel using 10% ethyl acetate concentrated to 77.3 g of brown oil The oil was redissolved in 400 ml of 10% ethyl acetate methylene chloride solution and chromatographed on 1.5 kg of silica gel A total of 9×250 ml fractions were collected