methyl (2R)-3-hydroxy-2-methylpropanoate

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

実験手順: (R)-3-Hydroxy-2-methyl-propionic acid methyl ester (8.60 g, 0.0728 mol) was dissolved in methylene chloride (200 mL, 3 mol), followed by N,N-diisopropylethylamine (25.4 mL, 0.146 mol). The reaction mixture was then cooled to −78° C., and chloromethyl methyl ether (9.48 mL, 0.0874 mol) was added dropwise. The reaction mixture was then allowed to warm up gradually over for 5 hours to 23° C., and quenched with Na2CO3 (sat). Organic layer was separated, and washed with water, brine, and then dried over Na2SO4. The to crude mixture was purified via chromatography (SiO2, 120 g, 0-30% ethyl acetate/hexanes) to give 10.3 g clear liquid product (87%). 1H NMR (CHLOROFORM-d) δ: 4.61 (s, 2H), 3.71 (m, 4H), 3.58 (dd, J=9.5, 5.5 Hz, 1H), 3.35 (s, 3H), 2.77 (m, 1H), 1.19 (d, J=7.0 Hz, 3H). to warm up gradually over for 5 hours to 23° C. quenched with Na2CO3 (sat) Organic layer was separated washed with water, brine dried over Na2SO4 The to crude mixture was purified via chromatography (SiO2, 120 g, 0-30% ethyl acetate/hexanes)

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

実験手順: (R)-3-Hydroxy-2-methyl-propionic acid methyl ester (8.60 g, 0.0728 mol) was dissolved in methylene chloride (200 mL, 3 mol), followed by N,N-diisopropylethylamine (25.4 mL, 0.146 mol). The reaction mixture was then cooled to −78° C., and chloromethyl methyl ether (9.48 mL, 0.0874 mol) was added dropwise. The reaction mixture was then allowed to warm up gradually over for 5 hours to 23° C., and quenched with Na2CO3 (sat). Organic layer was separated, and washed with water, brine, and then dried over Na2SO4. The to crude mixture was purified via chromatography (SiO2, 120 g, 0-30% ethyl acetate/hexanes) to give 10.3 g clear liquid product (87%). 1H NMR (CHLOROFORM-d) δ: 4.61 (s, 2H), 3.71 (m, 4H), 3.58 (dd, J=9.5, 5.5 Hz, 1H), 3.35 (s, 3H), 2.77 (m, 1H), 1.19 (d, J=7.0 Hz, 3H). to warm up gradually over for 5 hours to 23° C. quenched with Na2CO3 (sat) Organic layer was separated washed with water, brine dried over Na2SO4 The to crude mixture was purified via chromatography (SiO2, 120 g, 0-30% ethyl acetate/hexanes)

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

実験手順: An oven dried 1 L single-necked round bottom flask was equipped with a magnetic stir bar and then charged sequentially with 15.948 g (0.135 mol) of (R)-(−)-methyl-3-hydroxy-2-methylpropanoate, carbon tetrachloride (150 mL), cyclohexane (300 mL), and 35.796 g (0.142 mol) of benzyl 2,2,2-trichloroacetimidate. Trifluoromethanesulfonic acid (0.8 mL; 9.0 mmol) was added to the solution and the resulting mixture was stirred for 16 h at room temperature under an N2 atmosphere. The reaction mixture was then filtered and the filtrate concentrated in vacuo. The residue was redissolved in 150 mL EtOAc and extracted with saturated aqueous NaHCO3 (1×100 mL). The organic layer was washed with saturated NaCl, dried (MgSO4), filtered and evaporated. The residual oil was purified on a silica gel flash chromatography column eluted with 10% EtOAc-hexane. The purified fractions were combined and evaporated in vacuo to afford 20.787 (74%) of the title compound as an oil. MS (CI): m/e=209 (M+1). An oven dried 1 L single-necked round bottom flask was equipped with a magnetic stir bar The reaction mixture was then filtered the filtrate concentrated in vacuo The residue was redissolved in 150 mL EtOAc extracted with saturated aqueous NaHCO3 (1×100 mL) The organic layer was washed with saturated NaCl dried (MgSO4) filtered evaporated The residual oil was purified on a silica gel flash chromatography column eluted with 10% EtOAc-hexane evaporated in vacuo

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

実験手順: Methyl (R)-(−)-3-hydroxy-2-methylpropionate (30.81 g; 260.8 mmol) (Aldrich) was dissolved in dichloromethane (300 mL, dried over molecular sieves). Imidazole (25.11 g; 365.1 mmol) (Aldrich) and tert-butyl-diphenylsilyl chloride (68.00 mL; 261.5 mmol) (Aldrich) were added and the mixture was stirred at room temperature for 6 hours. The reaction was diluted with additional dichloromethane (300 mL), washed with water (2×150 mL) and brine (1×150 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to yield methyl (R)-(−)-3-(tert-butyl-diphenyl-silanyloxy)-2-methyl-propionate as an oil. (Yield 94.3 g). washed with water (2×150 mL) and brine (1×150 mL) dried over anhydrous sodium sulfate filtered concentrated

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

実験手順: Methyl (R)-(−)-3-hydroxy-2-methylpropionate (30.81 g; 260.8 mmol) (Aldrich) was dissolved in dichloromethane (300 mL, dried over molecular sieves). Imidazole (25.11 g; 365.1 mmol) (Aldrich) and tert-butyl-diphenylsilyl chloride (68.00 mL; 261.5 mmol) (Aldrich) were added and the mixture was stirred at room temperature for 6 hours. The reaction was diluted with additional dichloromethane (300 mL), washed with water (2×150 mL) and brine (1×150 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to yield methyl (R)-(−)-3-(tert-butyl-diphenyl-silanyloxy)-2-methyl-propionate as an oil. (Yield 94.3 g). washed with water (2×150 mL) and brine (1×150 mL) dried over anhydrous sodium sulfate filtered concentrated

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

実験手順: Methyl (R)-(−)-3-hydroxy-2-methylpropionate (30.81 g; 260.8 mmol) (Aldrich) was dissolved in dichloromethane (300 mL, dried over molecular sieves). Imidazole (25.11 g; 365.1 mmol) (Aldrich) and tert-butyl-diphenylsilyl chloride (68.00 mL; 261.5 mmol) (Aldrich) were added and the mixture was stirred at room temperature for 6 hours. The reaction was diluted with additional dichloromethane (300 mL), washed with water (2×150 mL) and brine (1×150 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to yield methyl (R)-(−)-3-(tert-butyl-diphenyl-silanyloxy)-2-methyl-propionate as an oil. (Yield 94.3 g). washed with water (2×150 mL) and brine (1×150 mL) dried over anhydrous sodium sulfate filtered concentrated

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

実験手順: An oven dried 1 L single-necked round bottom flask was equipped with a magnetic stir bar and then charged sequentially with 15.948 g (0.135 mol) of (R)-(-)-methyl-3-hydroxy-2-methylpropanoate, carbon tetrachloride (150 mL), cyclohexane (300 mL), and 35.796 g (0.142 mol) of benzyl 2,2,2-trichloroacetimidate. Trifluoromethanesulfonic acid (0.8 mL; 9.0 mmol) was added to the solution and the resulting mixture was stirred for 16 h at room temperature under an N2 atmosphere. The reaction mixture was then filtered and the filtrate concentrated in vacuo. The residue was redissolved in 150 mL EtOAc and extracted with saturated aqueous NaHCO3 (lxlOO mL). The organic layer was washed with saturated NaCl, dried (MgSO4), filtered and evaporated. The residual oil was purified on a silica gel flash chromatography column eluted with 10% EtOAc-hexane. The purified fractions were combined and evaporated in vacuo to afford 20.787g of the title compound as an oil. MS (CI): m/e=209 (M+1). An oven dried 1 L single-necked round bottom flask was equipped with a magnetic stir bar The reaction mixture was then filtered the filtrate concentrated in vacuo The residue was redissolved in 150 mL EtOAc extracted with saturated aqueous NaHCO3 (lxlOO mL) The organic layer was washed with saturated NaCl dried (MgSO4) filtered evaporated The residual oil was purified on a silica gel flash chromatography column eluted with 10% EtOAc-hexane evaporated in vacuo

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

実験手順: Imidazole (6.44 g, 42.8 mmol) and tert-butyldimethylsilyl chloride (6.05 g, 88.8 mmol) were added to a solution of (R)-3-hydroxy-2-methylpropionic acid methyl ester (5.0 g, 42.33 mmol) in dimethylformamide (50 mL), and the mixture was stirred at room temperature for 1.5 hours. Water was added to the reaction mixture, followed by extraction with hexane twice. The extract was then dried over magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure to give 9.3 g (95%) of the title compound as a colorless oil. followed by extraction with hexane twice The extract was then dried over magnesium sulfate After filtration the solvent was evaporated under reduced pressure

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

実験手順: (R)-3-Hydroxy-2-methyl-propionic acid methyl ester (8.60 g, 0.0728 mol) was dissolved in methylene chloride (200 mL, 3 mol), followed by N,N-diisopropylethylamine (25.4 mL, 0.146 mol). The reaction mixture was then cooled to −78° C., and chloromethyl methyl ether (9.48 mL, 0.0874 mol) was added dropwise. The reaction mixture was then allowed to warm up gradually over for 5 hours to 23° C., and quenched with Na2CO3 (sat). Organic layer was separated, and washed with water, brine, and then dried over Na2SO4. The to crude mixture was purified via chromatography (SiO2, 120g, 0-30% ethyl acetate/hexanes) to give 10.3 g clear liquid product (87%). 1H NMR (CHLOROFORM-d) δ: 4.61 (s, 2H), 3.71 (m, 4H), 3.58 (dd, J=9.5, 5.5 Hz, 1H), 3.35 (s, 3H), 2.77 (m, 1H), 1.19 (d, J=7.0 Hz, 3H). to warm up gradually over for 5 hours to 23° C. quenched with Na2CO3 (sat) Organic layer was separated washed with water, brine dried over Na2SO4 The to crude mixture was purified via chromatography (SiO2, 120g, 0-30% ethyl acetate/hexanes)

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

実験手順: Methyl (R)-(−)-3-hydroxy-2-methylpropionate (0.82 g, 6.92 mmol) (Aldrich) was dissolved in dichloromethane (8 mL, dried over molecular sieves). Imidazole (0.67 g, 9.68 mmol) (Aldrich) was added. When all had dissolved, tert-butyldiphenysilyl chloride (1.80 mL, 6.92 mmol) (Aldrich) was added and the mixture was stirred at ambient temperature for 3 hours. The reaction was diluted with additional dichloromethane, washed with water and brine, dried over anhydrous sodium sulfate and concentrated to give methyl (R)-3-(tert-butyl-diphenyl-silanyloxy)-2-methyl-propionate as an oil. (Yield 2.42 g, 98%). When all had dissolved washed with water and brine dried over anhydrous sodium sulfate concentrated

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

実験手順: (R)-3-Hydroxy-2-methyl-propionic acid methyl ester (8.60 g, 0.0728 mol) was dissolved in methylene chloride (200 mL, 3 mol), followed by N,N-diisopropylethylamine (25.4 mL, 0.146 mol). The reaction mixture was then cooled to −78° C., and chloromethyl methyl ether (9.48 mL, 0.0874 mol) was added dropwise. The reaction mixture was then allowed to warm up gradually over for 5 hours to 23° C., and quenched with Na2CO3 (sat). Organic layer was separated, and washed with water, brine, and then dried over Na2SO4. The to crude mixture was purified via chromatography (SiO2, 120 g, 0-30% ethyl acetate/hexanes) to give 10.3 g clear liquid product (87%). 1H NMR (CHLOROFORM-d) δ: 4.61 (s, 2H), 3.71 (m, 4H), 3.58 (dd, J=9.5, 5.5 Hz, 1H), 3.35 (s, 3H), 2.77 (m, 1H), 1.19 (d, J=7.0 Hz, 3H). to warm up gradually over for 5 hours to 23° C. quenched with Na2CO3 (sat) Organic layer was separated washed with water, brine dried over Na2SO4 The to crude mixture was purified via chromatography (SiO2, 120 g, 0-30% ethyl acetate/hexanes)

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

実験手順: An oven dried 1 L single-necked round bottom flask was equipped with a magnetic stir bar and then charged sequentially with 15.948 g (0.135 mol) of (R)-(−)-methyl-3-hydroxy-2-methylpropanoate, carbon tetrachloride (150 mL), cyclohexane (300 mL), and 35.796 g (0.142 mol) of benzyl 2,2,2-trichloroacetimidate. Trifluoromethanesulfonic acid (0.8 mL; 9.0 mmol) was added to the solution and the resulting mixture was stirred for 16 h at room temperature under an N2 atmosphere. The reaction mixture was then filtered and the filtrate concentrated in vacuo. The residue was redissolved in 150 mL EtOAc and extracted with saturated aqueous NaHCO3 (1×100 mL). The organic layer was washed with saturated NaCl, dried (MgSO4), filtered and evaporated. The residual oil was purified on a silica gel flash chromatography column eluted with 10% EtOAc-hexane. The purified fractions were combined and evaporated in vacuo to afford 20.787 (74%) of the title compound as an oil. MS (CI): m/e=209 (M+1). An oven dried 1 L single-necked round bottom flask was equipped with a magnetic stir bar The reaction mixture was then filtered the filtrate concentrated in vacuo The residue was redissolved in 150 mL EtOAc extracted with saturated aqueous NaHCO3 (1×100 mL) The organic layer was washed with saturated NaCl dried (MgSO4) filtered evaporated The residual oil was purified on a silica gel flash chromatography column eluted with 10% EtOAc-hexane evaporated in vacuo