4-hydroxy-3-(hydroxymethyl)-3-methylbutan-2-one

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a one liter three neck flask equipped with a mechanical stirrer and under nitrogen were added triphosgene (37.0 g), 3,3-dihydroxymethyl-2-butanone (50 g) and THF (300 mL). The resulting mixture was stirred until a homogeneous solution resulted. This homogeneous solution was cooled to -78° C. Triethylamine (75.0 g) was added to the this solution over 30 min. The cold bath was removed and the reaction allowed to warm to room temperature. After stirring for one hour at room temperature the triethylamine/HCl salt was removed by filtration and the filtrate pass through a silica gel plug. The solvent was removed under reduced pressure resulting in an off white product. This product was then washed with hot ether giving a white solid. NMR analysis indicated that the product contained a small amount of triethylamine/HCl salt, thus the material was dissolved in dichloromethane and washed with water affording 15.02 g of material. 1H NMR (CDCl3) ppm: 4.70 (ab doublet, 2H), 4.20 (ab doublet, 2H), 2.3 (S, 3H), 1.25 (S, 3H). resulted The cold bath was removed to warm to room temperature After stirring for one hour at room temperature the triethylamine/HCl salt was removed by filtration The solvent was removed under reduced pressure resulting in an off white product This product was then washed with hot ether giving a white solid thus the material was dissolved in dichloromethane washed with water affording 15.02 g of material

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

実験手順: 2,2-Dimethoxypropane (418.0 g, 4.0 mol) and The 3,3-Bis(hydroxymethyl)-2-butanone (264.32 g, 2.0 mol) were mixed together in 1 liter of dichloromethane. Amberlyst-15 ion exchange resin (strongly acidic; 40.0 g) was added to the solution and the resultant suspension stirred vigorously at room temperature. After 1 hr TLC indicated no starting material and complete conversion to the desired product. The spent resin was separated from the solution by filtration through a thick pad of anhydrous potassium carbonate. Subsequently, the residual dimethoxypropane and dichloromethane were removed in vactio to give a pale straw-colored liquid. The liquid solidified upon standing as large clear, colorless crystals, m.p. 48-50° C.; 300 g, 87.1% of theoretical yield; H-NMR spectra were consistent. Elemental Analysis calculated for C9H16O3: C, 62.77; H, 9.36. Found: C, 62.00; H. 9.01. 40.0 g) was added to the solution

反応条件: temp:12.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Butanone (216 g, 3.0 mol) and 30% formalin (600 g, 6.0 mol) were added simultaneously, but separately, to an aqueous calcium hydroxide solution (1.89 g, 0.255 mol) in a 3-liter flask during a 5-min. period. The solution was stirred vigorously for 6 hr at 10-15° C. Another portion of calcium hydroxide (0.4 g, 0.0054 mol) was added and the reaction mixture stirred another 6 hr at ambient conditions. Subsequently, the solution was filtered and neutralized with dry ice. The solution was concentrated at reduced pressure to yield a cloudy syrup containing insoluble calcium carbonate. The viscous product was dissolved in a minimum amount of ethyl acetate and filtered to remove traces of calcium carbonate, and the ethyl acetate was removed in vacuo to yield a water white liquid. The residue was slurried in 3 liters of ligroin and the mixture heated to boiling with good stirring for 10 min. The solution/suspension was allowed to cool/settle for 2 hr., after which time the ligroin was decanted from the liquid product. This procedure was repeated once more except that the solution was allowed to stand overnight in a freezer. The ligroin was decanted and the solid recovered. The 3,3-Bis(hydroxymethyl)-2-butanone was used without further purification. Analytical samples were prepared by recrystallization from chloroform and petroleum ether; m.p. 60° C.; 753 g, 95% of theoretical yield; H-NMR spectra were consistent. the reaction mixture stirred another 6 hr at ambient conditions Subsequently, the solution was filtered The solution was concentrated at reduced pressure to yield a cloudy syrup filtered to remove traces of calcium carbonate the ethyl acetate was removed in vacuo to yield a water white liquid the mixture heated with good stirring for 10 min to cool/settle for 2 hr , after which time the ligroin was decanted from the liquid product to stand overnight in a freezer The ligroin was decanted the solid recovered The 3,3-Bis(hydroxymethyl)-2-butanone was used without further purification Analytical samples were prepared by recrystallization from chloroform and petroleum ether

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

実験手順: A solution of 3,3-bis(hydroxymethyl)-2-butanone (66.1parts) and s-trioxane (27 parts) in toluene (250 parts) containing p-toluenesulfonic acid (1.9 parts) is held under reflux while water of reaction is continuously removed (ca. 0.5 hr) by a Dean-Stark trap. The solution is cooled, neutralized by stirring with solid sodium bicarbonate and filtered Toluene is removed in vacuo and the residue distilled at 50-55° C. and 0.6 mm Hg. Proton NMR and combustion analysis are consistent with those values predicted for the desired product. Combustion Analysis for C7H12O3 --Calculated: C, 58.3%; H, 8.4%. Found: C, 57.9%; H, 8.2%. is continuously removed (ca. 0.5 hr) by a Dean-Stark trap The solution is cooled filtered Toluene is removed in vacuo the residue distilled at 50-55° C.

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

実験手順: 3,3-bis(Hydroxymethyl)-2-butanone (39.7 parts) and 4-nitrobenzaldehyde (30.2 parts) are combined in toluene (300 parts) containing p-toluenesulfonic acid, (p-TSA), (1.0 part) and the mixture held under reflux until a theoretical amount of water is removed by a Dean-Stark moisture trap. The solution is concentrated in vacuo and the residue washed once with dilute sodium bicarbonate solution. The product is recrystallized from ethyl acetate-heptane mixed solvent to give colorless needles, m.p. 101-102.5° C. Proton NMR and combustion analysis are consistent with those values predicted for the desired product. Combustion Analysis for C13H15NO5 --Calculated: C, 58.9%; H, 5.7%; N, 5.3%. Found: C, 59.0%; H, 5.8%; N, 5.4%. is removed by a Dean-Stark moisture trap The solution is concentrated in vacuo the residue washed once with dilute sodium bicarbonate solution The product is recrystallized from ethyl acetate-heptane mixed solvent to give colorless needles, m.p. 101-102.5° C

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

実験手順: 2,2-Dimethoxypropane (418 parts), 3,3-bis(hydroxymethyl)-2-butanone (265 parts) and Amberlyst-15®, (40 parts) are combined in dichloromethane (1,320 parts) and the resultant suspension stirred vigorously at room temperature, ca. 1 hr. The spent resin is separated from the solution by filtration and the residual solvents removed in vacuo to yield a pale straw-colored liquid which can solidify upon standing. Yield is 87% of theory and analytical samples are recrystallized from ethyl ether, m.p. 48-50° C. Proton NMR and combustion analysis are consistent with those values predicted for the desired product. Combustion Analysis for C9H16O3 --Calculated: C, 62.8%; H, 9.4%. Found: C, 62.0%; H, 9.0%. The spent resin is separated from the solution by filtration the residual solvents removed in vacuo to yield a pale straw-colored liquid which Yield is 87% of theory and analytical samples are recrystallized from ethyl ether, m.p. 48-50° C

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a one liter three neck flask equipped with a mechanical stirrer and under nitrogen were added triphosgene (37.0 g), 3,3-dihydroxymethyl-2-butanone (50 g) and THF (300 mL). The resulting mixture was stirred until a homogeneous solution resulted. This homogeneous solution was cooled to -78° C. Triethylamine (75.0 g) was added to the this solution over 30 min. The cold bath was removed and the reaction allowed to warm to room temperature. After stirring for one hour at room temperature the triethylamine/HCl salt was removed by filtration and the filtrate pass through a silica gel plug. The solvent was removed under reduced pressure resulting in an off white product. This product was then washed with hot ether giving a white solid. NMR analysis indicated that the product contained a small amount of triethylamine/HCl salt, thus the material was dissolved in dichloromethane and washed with water affording 15.02 g of material. 1H NMR (CDCl3) ppm: 4.70 (ab doublet, 2H), 4.20 (ab doublet, 2H), 2.3 (S, 3H), 1.25 (S, 3H). resulted The cold bath was removed to warm to room temperature After stirring for one hour at room temperature the triethylamine/HCl salt was removed by filtration The solvent was removed under reduced pressure resulting in an off white product This product was then washed with hot ether giving a white solid thus the material was dissolved in dichloromethane washed with water affording 15.02 g of material

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a one liter three neck flask equipped with a mechanical stirrer and under nitrogen were added triphosgene (37.0 g), 3,3-dihydroxymethyl-2-butanone (50 g) and THF (300 mL). The resulting mixture was stirred until a homogeneous solution resulted. This homogeneous solution was cooled to -78° C. Triethylamine (75.0 g) was added to the this solution over 30 min. The cold bath was removed and the reaction allowed to warm to room temperature. After stirring for one hour at room temperature the triethylamine/HCl salt was removed by filtration and the filtrate pass through a silica gel plug. The solvent was removed under reduced pressure resulting in an off white product. This product was then washed with hot ether giving a white solid. NMR analysis indicated that the product contained a small amount of triethylamine/HCl salt, thus the material was dissolved in dichloromethane and washed with water affording 15.02 g of material. 1H NMR (CDCl3) ppm: 4.70 (ab doublet, 2H), 4.20 (ab doublet, 2H), 2.3 (S, 3H), 1.25 (S, 3H). resulted The cold bath was removed to warm to room temperature After stirring for one hour at room temperature the triethylamine/HCl salt was removed by filtration The solvent was removed under reduced pressure resulting in an off white product This product was then washed with hot ether giving a white solid thus the material was dissolved in dichloromethane washed with water affording 15.02 g of material

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

実験手順: 66 g (0.5 mol) of 3-oxo-2,2-bis-[hydroxymethyl]-butane (for the preparation, see Beilstein H 1, E III 3306, IV 4132 and J. Chem. Soc., London 1932, 2671) were dissolved in 300 ml of 1,2-dichloroethane, 114.5 g (1 mol) of methanesulphonyl chloride were added dropwise and 158 g (2 mol) of pyridine were added dropwise at 0° to 5° C. The reaction mixture was stirred for a further 15 hours at room temperature and the batch was then introduced into 600 ml of ice-water and 100 ml of concentrated hydrochloric acid. A solid precipitated out and this was filtered off. The aqueous phase was extracted with 1 liter of methylene chloride; the solid was dissolved in the methylene chloride phase, the organic phase was dried over sodium sulphate, the solvent was distilled off under a waterpump vacuum and the residue was suspended in 200 ml of ether. 100 g (about 70% of theory) of 2-acetyl-2-methyl-propane-1,3-diol bismethanesulphonate with a melting point of 105° to 108° C. were obtained. ##STR12## A solid precipitated out this was filtered off The aqueous phase was extracted with 1 liter of methylene chloride the solid was dissolved in the methylene chloride phase the organic phase was dried over sodium sulphate the solvent was distilled off under a waterpump vacuum

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

実験手順: 66 g (0.5 mol) of 3-oxo-2,2-bis-[hydroxymethyl]-butane (for the preparation, see Beilstein H 1, E III 3306, IV 4132 and J. Chem. Soc., London 1932, 2671) were dissolved in 300 ml of 1,2-dichloroethane, 114.5 g (1 mol) of methanesulphonyl chloride were added dropwise and 158 g (2 mol) of pyridine were added dropwise at 0° to 5° C. The reaction mixture was stirred for a further 15 hours at room temperature and the batch was then introduced into 600 ml of ice-water and 100 ml of concentrated hydrochloric acid. A solid precipitated out and this was filtered off. The aqueous phase was extracted with 1 liter of methylene chloride; the solid was dissolved in the methylene chloride phase, the organic phase was dried over sodium sulphate, the solvent was distilled off under a waterpump vacuum and the residue was suspended in 200 ml of ether. 100 g (about 70% of theory) of 2-acetyl-2-methyl-propane-1,3-diol bismethanesulphonate with a melting point of 105° to 108° C. were obtained. ##STR12## A solid precipitated out this was filtered off The aqueous phase was extracted with 1 liter of methylene chloride the solid was dissolved in the methylene chloride phase the organic phase was dried over sodium sulphate the solvent was distilled off under a waterpump vacuum

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

実験手順: 66 g (0.5 mol) of 3-oxo-2,2-bis-[hydroxymethyl]-butane (for the preparation, see Beilstein H 1, E III 3306, IV 4132 and J. Chem. Soc., London 1932, 2671) were dissolved in 300 ml of 1,2-dichloroethane, 114.5 g (1 mol) of methanesulphonyl chloride were added dropwise and 158 g (2 mol) of pyridine were added dropwise at 0° to 5° C. The reaction mixture was stirred for a further 15 hours at room temperature and the batch was then introduced into 600 ml of ice-water and 100 ml of concentrated hydrochloric acid. A solid precipitated out and this was filtered off. The aqueous phase was extracted with 1 liter of methylene chloride; the solid was dissolved in the methylene chloride phase, the organic phase was dried over sodium sulphate, the solvent was distilled off under a waterpump vacuum and the residue was suspended in 200 ml of ether. 100 g (about 70% of theory) of 2-acetyl-2-methyl-propane-1,3-diol bismethanesulphonate with a melting point of 105° to 108° C. were obtained. ##STR12## A solid precipitated out this was filtered off The aqueous phase was extracted with 1 liter of methylene chloride the solid was dissolved in the methylene chloride phase the organic phase was dried over sodium sulphate the solvent was distilled off under a waterpump vacuum

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

実験手順: 66 g (0.5 mol) of 3-oxo-2,2-bis-(hydroxymethyl)-butane (for the preparation, see Beilstein H 1, E III 3306, IV 4132 and J.Chem.Soc., London, 1932, 2671) were dissolved in 300 ml of 1,2-dichloroethane, 114.5 g (1 mol) of methanesulphonic acid chloride were added dropwise, and 158 g (2 mol) of pyridine were added dropwise at 0° to 5° C. The mixture was subsequently stirred at room temperature for 15 hours and then poured onto 600 ml of ice-water and 100 ml of concentrated hydrochloric acid. A solid thereby precipitated and was filtered off. The aqueous phase was extracted with 1,000 ml of methylene chloride; the solid was dissolved in the methylene chloride phase, the organic phase was dried over sodium sulphate, the solvent was distilled off under a waterpump vacuum and the residue was suspended in 200 ml of ether. The residue was filtered off and washed with 100 ml of ether. 100 g (about 70% of theory) of 2-acetyl-2-methylpropane-1,3-diol bismethanesulphonate of melting point 105°-108° C. were obtained. ##STR71## A solid thereby precipitated was filtered off The aqueous phase was extracted with 1,000 ml of methylene chloride the solid was dissolved in the methylene chloride phase the organic phase was dried over sodium sulphate the solvent was distilled off under a waterpump vacuum The residue was filtered off washed with 100 ml of ether