2-甲基-2-苯基丙烷-1,3-二醇

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

实验步骤: 2-Methyl-2-phenylpropane-1,3-diol (3.37 g, 20.3 mmol) was dissolved in DMF, NaH (812 mg, 60%, 20.3 mmol) was added and the mixture was stirred at room temperature for 30 minutes. A DMF solution of 3,5-bistrifluoromethylbenzyl bromide (6.23 g, 20.3 mmol) was added in one portion and stirred for another 1 hour before it was quenched with water and extracted with ethyl acetate. The organic phase was washed with brine and dried with Na2SO4 before being concentrated. The crude product was purified by silica flash chromatography using 15% ethyl acetate in hexanes to yield 4.2 grams (52.8%) of the desired mono-alkylated product. 1H NMR (500 MHz, CDCl3) δ: 1.40 (s, 3 H) 1.78 (s, 1 H) 3.72 (d, J=9.16 Hz, 1 H) 3.82 (d, J=9.16 Hz, 1 H) 3.89 (m, 2 H) 4.64 (s, 2 H) 7.26 (m, 1 H) 7.37 (m, 4 H) 7.72 (s, 2 H) 7.79 (s, 1 H). stirred for another 1 hour before it was quenched with water extracted with ethyl acetate The organic phase was washed with brine dried with Na2SO4 before being concentrated The crude product was purified by silica flash chromatography to yield 4.2 grams (52.8%) of the desired mono-alkylated product

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

实验步骤: Diethyl diphenylmalonate (10 g, 42.4 mmol) and iodomethane (6.6 g, 46.6 mmol) was mixed in anhydrous THF (200 ml) at room temperature before NaH powder was added in several portions. The reaction finished instantly with release of heat. After cooled down to room temperature, aqueous NaHCO3 solution was added to quench the reaction. The mixture was extracted with ethyl acetate, washed with water, brine, dried with Na2SO4 and concentrated. A clean NMR spectrum of the crude product identified it as the desired product. 1H NMR (500 MHz, CDCl3) δ ppm 1.26 (t, J=7.17 Hz, 6 H) 4.24 (m, 3 H) 7.34 (m, 5 H). The crude product was then dissolved in anhydrous THF (200 ml) and cooled to −20° C. Lithium aluminun hydride (42.4 mmol) was added via dropping funnel within 10 minutes. The reaction mixture was warmed up naturally to room temperature and quenched with ethyl acetate and water. The orgamic layer was washed with brine and dried with Na2SO4 before being concentated in-vacuo. The crude product was purified by silica flash chromatography using 50% ethyl acetate in hexanes to yield 4.35 grams (62% in two steps) of the desired product. 1H NMR (500 MHz, CDCl3) δ: 3.85 (m, 3 H) 3.98 (d, J=10.99 Hz, 2 H) 7.27 (m, 1 H) 7.38 (t, J=7.93 Hz, 2 H) 7.44 (m, 2 H). was added in several portions of heat to quench the reaction The mixture was extracted with ethyl acetate washed with water, brine dried with Na2SO4 concentrated The crude product was then dissolved in anhydrous THF (200 ml) cooled to −20° C within 10 minutes The reaction mixture was warmed up naturally to room temperature quenched with ethyl acetate and water The orgamic layer was washed with brine dried with Na2SO4 The crude product was purified by silica flash chromatography

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

实验步骤: Using the method described in Example 1(b), 1.2 parts per hour of a 50 percent strength by weight solution of 2-methyl-2-phenyl-3-hydroxypropanal in a 1:1 water-methanol mixture are hydrogenated, over the catalyst prepared as described in Example 1(a), at 130° C. and 30 bar, with a throughput of 0.3 part of 2-methyl-2-phenyl-3-hydroxypropanol per liter of catalyst per hour. The conversion is over 99 percent. The hydrogenated material is fractionated through a packed column. After first runnings of water, methanol, 2-phenylpropanol and 2-methyl-2-phenyl-3-hydroxypropanal, 2-methyl-2-phenyl-propane-1,3-diol, of boiling point 143°-145° C./1 mbar (melting point 80°-82° C.), is obtained in an amount corresponding to 0.5405 part per hour. This is equivalent to a yield of 89% of theory, based on starting material. prepared as described in Example 1(a), at 130° C.

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

实验步骤: 2-Methyl-2-phenylpropane-1,3-diol (3.37 g, 20.3 mmol) was dissolved in DMF, NaH (812 mg, 60%, 20.3 mmol) was added and the mixture was stirred at room temperature for 30 minutes. A DMF solution of 3,5-bistrifluoromethylbenzyl bromide (6.23 g, 20.3 mmol) was added in one portion and stirred for another 1 hour before it was quenched with water and extracted with ethyl acetate. The organic phase was washed with brine and dried with Na2SO4 before being concentrated. The crude product was purified by silica flash chromatography using 15% ethyl acetate in hexanes to yield 4.2 grams (52.8%) of the desired mono-alkylated product. 1H NMR (500 MHz, CDCl3) δ: 1.40 (s, 3 H) 1.78 (s, 1 H) 3.72 (d, J=9.16 Hz, 1 H) 3.82 (d, J=9.16 Hz, 1 H) 3.89 (m, 2 H) 4.64 (s, 2 H) 7.26 (m, 1 H) 7.37 (m, 4 H) 7.72 (s, 2 H) 7.79 (s, 1 H). stirred for another 1 hour before it was quenched with water extracted with ethyl acetate The organic phase was washed with brine dried with Na2SO4 before being concentrated The crude product was purified by silica flash chromatography to yield 4.2 grams (52.8%) of the desired mono-alkylated product

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

实验步骤: Diethyl diphenylmalonate (10 g, 42.4 mmol) and iodomethane (6.6 g, 46.6 mmol) was mixed in anhydrous THF (200 ml) at room temperature before NaH powder was added in several portions. The reaction finished instantly with release of heat. After cooled down to room temperature, aqueous NaHCO3 solution was added to quench the reaction. The mixture was extracted with ethyl acetate, washed with water, brine, dried with Na2SO4 and concentrated. A clean NMR spectrum of the crude product identified it as the desired product. 1H NMR (500 MHz, CDCl3) δ ppm 1.26 (t, J=7.17 Hz, 6 H) 4.24 (m, 3 H) 7.34 (m, 5 H). The crude product was then dissolved in anhydrous THF (200 ml) and cooled to −20° C. Lithium aluminun hydride (42.4 mmol) was added via dropping funnel within 10 minutes. The reaction mixture was warmed up naturally to room temperature and quenched with ethyl acetate and water. The orgamic layer was washed with brine and dried with Na2SO4 before being concentated in-vacuo. The crude product was purified by silica flash chromatography using 50% ethyl acetate in hexanes to yield 4.35 grams (62% in two steps) of the desired product. 1H NMR (500 MHz, CDCl3) δ: 3.85 (m, 3 H) 3.98 (d, J=10.99 Hz, 2 H) 7.27 (m, 1 H) 7.38 (t, J=7.93 Hz, 2 H) 7.44 (m, 2 H). was added in several portions of heat to quench the reaction The mixture was extracted with ethyl acetate washed with water, brine dried with Na2SO4 concentrated The crude product was then dissolved in anhydrous THF (200 ml) cooled to −20° C within 10 minutes The reaction mixture was warmed up naturally to room temperature quenched with ethyl acetate and water The orgamic layer was washed with brine dried with Na2SO4 The crude product was purified by silica flash chromatography

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

实验步骤: Using the method described in Example 1(b), 1.2 parts per hour of a 50 percent strength by weight solution of 2-methyl-2-phenyl-3-hydroxypropanal in a 1:1 water-methanol mixture are hydrogenated, over the catalyst prepared as described in Example 1(a), at 130° C. and 30 bar, with a throughput of 0.3 part of 2-methyl-2-phenyl-3-hydroxypropanol per liter of catalyst per hour. The conversion is over 99 percent. The hydrogenated material is fractionated through a packed column. After first runnings of water, methanol, 2-phenylpropanol and 2-methyl-2-phenyl-3-hydroxypropanal, 2-methyl-2-phenyl-propane-1,3-diol, of boiling point 143°-145° C./1 mbar (melting point 80°-82° C.), is obtained in an amount corresponding to 0.5405 part per hour. This is equivalent to a yield of 89% of theory, based on starting material. prepared as described in Example 1(a), at 130° C.

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

实验步骤: 2-Methyl-2-phenylpropane-1,3-diol (3.37 g, 20.3 mmol) was dissolved in DMF, NaH (812 mg, 60%, 20.3 mmol) was added and the mixture was stirred at room temperature for 30 minutes. A DMF solution of 3,5-bistrifluoromethylbenzyl bromide (6.23 g, 20.3 mmol) was added in one portion and stirred for another 1 hour before it was quenched with water and extracted with ethyl acetate. The organic phase was washed with brine and dried with Na2SO4 before being concentrated. The crude product was purified by silica flash chromatography using 15% ethyl acetate in hexanes to yield 4.2 grams (52.8%) of the desired mono-alkylated product. 1H NMR (500 MHz, CDCl3) δ: 1.40 (s, 3 H) 1.78 (s, 1 H) 3.72 (d, J=9.16 Hz, 1 H) 3.82 (d, J=9.16 Hz, 1 H) 3.89 (m, 2 H) 4.64 (s, 2 H) 7.26 (m, 1 H) 7.37 (m, 4 H) 7.72 (s, 2 H) 7.79 (s, 1 H). stirred for another 1 hour before it was quenched with water extracted with ethyl acetate The organic phase was washed with brine dried with Na2SO4 before being concentrated The crude product was purified by silica flash chromatography to yield 4.2 grams (52.8%) of the desired mono-alkylated product

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

实验步骤: Diethyl diphenylmalonate (10 g, 42.4 mmol) and iodomethane (6.6 g, 46.6 mmol) was mixed in anhydrous THF (200 ml) at room temperature before NaH powder was added in several portions. The reaction finished instantly with release of heat. After cooled down to room temperature, aqueous NaHCO3 solution was added to quench the reaction. The mixture was extracted with ethyl acetate, washed with water, brine, dried with Na2SO4 and concentrated. A clean NMR spectrum of the crude product identified it as the desired product. 1H NMR (500 MHz, CDCl3) δ ppm 1.26 (t, J=7.17 Hz, 6 H) 4.24 (m, 3 H) 7.34 (m, 5 H). The crude product was then dissolved in anhydrous THF (200 ml) and cooled to −20° C. Lithium aluminun hydride (42.4 mmol) was added via dropping funnel within 10 minutes. The reaction mixture was warmed up naturally to room temperature and quenched with ethyl acetate and water. The orgamic layer was washed with brine and dried with Na2SO4 before being concentated in-vacuo. The crude product was purified by silica flash chromatography using 50% ethyl acetate in hexanes to yield 4.35 grams (62% in two steps) of the desired product. 1H NMR (500 MHz, CDCl3) δ: 3.85 (m, 3 H) 3.98 (d, J=10.99 Hz, 2 H) 7.27 (m, 1 H) 7.38 (t, J=7.93 Hz, 2 H) 7.44 (m, 2 H). was added in several portions of heat to quench the reaction The mixture was extracted with ethyl acetate washed with water, brine dried with Na2SO4 concentrated The crude product was then dissolved in anhydrous THF (200 ml) cooled to −20° C within 10 minutes The reaction mixture was warmed up naturally to room temperature quenched with ethyl acetate and water The orgamic layer was washed with brine dried with Na2SO4 The crude product was purified by silica flash chromatography