methyl 3-(2-methoxyethoxy)-2,2-dimethylpropanoate

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

実験手順: A solution of 3-(2-methoxy-ethoxy)-2,2-dimethyl-propionic acid methyl ester (3.08 g, 16.21 mmol) and acetonitrile (1.19 mL, 22.69 mmol) in toluene (6 mL) is added dropwise to the refluxing suspension of 60% sodium hydride in mineral oil (907.6 mg, 22.69 mmol) in toluene (18 mL). After the addition, the reaction mixture is stirred at reflux for 3 h. After this time, the reaction mixture is cooled to room temperature and the aqueous layer is neutralized to pH˜7 by adding 1M aqueous HCl solution. The aqueous layer is extracted with ethyl acetate 3 times. The organic layers are combined, washed with brine, dried over Na2SO4 and filtered. The filtrate is concentrated under reduced pressure to yield the title compound. Yield: 94.2%. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.20 (6H, s), 3.38 (3H, s), 3.47 (2H, s), 3.50-3.55 (2H, m), 3.57-3.62 (2H, m), 3.80 (2H, s). After the addition at reflux for 3 h The aqueous layer is extracted with ethyl acetate 3 times washed with brine dried over Na2SO4 filtered The filtrate is concentrated under reduced pressure

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

実験手順: To a solution of methyl 3-hydroxy-2,2-dimethyl-propionate (2.72 mL, 21.28 mmol) in 3 mL of DMF is added 60% sodium hydride in mineral oil (1.70 g, 42.56 mmol) in one portion, followed by the addition of 2-bromoethyl methyl ether (4.0 mL, 42.56 mmol). The reaction mixture is stirred at room temperature for 3 hs. After this time, the reaction mixture is quenched with saturated aqueous NH4Cl solution and the product is extracted with DCM twice. The organics are combined and washed with water 4 times then brine, dried over Na2SO4, filtered and concentrated under reduced pressure to yield the title compound. Yield: 76%; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.19 (6H, s), 3.36 (3H, s), 3.48 (2H, s), 3.48-3.52 (2H, m), 3.54-3.60 (2H, m), 3.67 (3H, s). After this time, the reaction mixture is quenched with saturated aqueous NH4Cl solution the product is extracted with DCM twice washed with water 4 times brine, dried over Na2SO4 filtered concentrated under reduced pressure

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

実験手順: A solution of 3-(2-methoxy-ethoxy)-2,2-dimethyl-propionic acid methyl ester (3.08 g, 16.21 mmol) and acetonitrile (1.19 mL, 22.69 mmol) in toluene (6 mL) is added dropwise to the refluxing suspension of 60% sodium hydride in mineral oil (907.6 mg, 22.69 mmol) in toluene (18 mL). After the addition, the reaction mixture is stirred at reflux for 3 h. After this time, the reaction mixture is cooled to room temperature and the aqueous layer is neutralized to pH˜7 by adding 1M aqueous HCl solution. The aqueous layer is extracted with ethyl acetate 3 times. The organic layers are combined, washed with brine, dried over Na2SO4 and filtered. The filtrate is concentrated under reduced pressure to yield the title compound. Yield: 94.2%. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.20 (6H, s), 3.38 (3H, s), 3.47 (2H, s), 3.50-3.55 (2H, m), 3.57-3.62 (2H, m), 3.80 (2H, s). After the addition at reflux for 3 h The aqueous layer is extracted with ethyl acetate 3 times washed with brine dried over Na2SO4 filtered The filtrate is concentrated under reduced pressure

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

実験手順: To a solution of methyl 3-hydroxy-2,2-dimethyl-propionate (2.72 mL, 21.28 mmol) in 3 mL of DMF is added 60% sodium hydride in mineral oil (1.70 g, 42.56 mmol) in one portion, followed by the addition of 2-bromoethyl methyl ether (4.0 mL, 42.56 mmol). The reaction mixture is stirred at room temperature for 3 hs. After this time, the reaction mixture is quenched with saturated aqueous NH4Cl solution and the product is extracted with DCM twice. The organics are combined and washed with water 4 times then brine, dried over Na2SO4, filtered and concentrated under reduced pressure to yield the title compound. Yield: 76%; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.19 (6H, s), 3.36 (3H, s), 3.48 (2H, s), 3.48-3.52 (2H, m), 3.54-3.60 (2H, m), 3.67 (3H, s). After this time, the reaction mixture is quenched with saturated aqueous NH4Cl solution the product is extracted with DCM twice washed with water 4 times brine, dried over Na2SO4 filtered concentrated under reduced pressure

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

実験手順: A suspension of methyl 3-(2-methoxyethoxy)-2,2-dimethylpropanoate (39) (1.83 g, 9.62 mmol) and KOH (2.16 g, 38.5 mmol) in water (20 mL) was stirred at RT for 3 days. The aqueous layer was washed with DCM (3×20 mL) and acidified to pH 1-2 with 6 M HCl (aq.) and extracted with DCM (3×20 mL). The combined organics were dried (MgSO4), filtered and concentrated in vacuo to afford 3-(2-methoxyethoxy)-2,2-dimethylpropanoic acid (40) (1.62 g, 96%) as colourless oil: 1H NMR (400 MHz, CDCl3) δ: 3.67-3.65 (m, 2H), 3.56-3.54 (m, 2H), 3.51 (s, 2H), 3.38 (s, 3H), 1.23 (s, 6H). The aqueous layer was washed with DCM (3×20 mL) extracted with DCM (3×20 mL) The combined organics were dried (MgSO4) filtered concentrated in vacuo

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

実験手順: Sodium hydride (60% wt in oil) (3.14 g, 78 mmol) was added to a stirred solution of methyl 3-hydroxy-2,2-dimethylpropanoate (5 mL, 39.2 mmol) in DMF (5.6 mL) at 0° C., after 5 min 1-bromo-2-methoxyethane (7.4 mL, 78 mmol) was added dropwise, and the reaction mixture was allowed to stir for 3 h. The reaction was quenched with sat. NH4Cl (aq.) (30 mL) and the aqueous layer was extracted with DCM (2×50 mL), the combined organic layers were dried (MgSO4), filtered and concentrated in vacuo. The crude oil was dissolved in EtOAc (125 mL) and washed with water (3×40 mL), dried (MgSO4), filtered and concentrated in vacuo. The material was purified by vacuum distillation (68-69° C., 4.4 mbar) to afford methyl 3-(2-methoxyethoxy)-2,2-dimethylpropanoate (39) (1.83 g, 25%) as a colourless oil: 1H NMR (400 MHz, CDCl3) δ: 3.68 (s, 3H), 3.60-3.58 (m, 2H), 3.52-3.50 (m, 2H), 3.49 (s, 2H), 3.37 (s, 3H), 1.19 (s, 6H). was added dropwise The reaction was quenched with sat. NH4Cl (aq.) (30 mL) the aqueous layer was extracted with DCM (2×50 mL) the combined organic layers were dried (MgSO4) filtered concentrated in vacuo The crude oil was dissolved in EtOAc (125 mL) washed with water (3×40 mL) dried (MgSO4) filtered concentrated in vacuo The material was purified by vacuum distillation (68-69° C., 4.4 mbar)

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

実験手順: A solution of 3-(2-methoxy-ethoxy)-2,2-dimethyl-propionic acid methyl ester (3.08 g, 16.21 mmol) and acetonitrile (1.19 mL, 22.69 mmol) in toluene (6 mL) is added dropwise to the refluxing suspension of 60% sodium hydride in mineral oil (907.6 mg, 22.69 mmol) in toluene (18 mL). After the addition, the reaction mixture is stirred at reflux for 3 h. After this time, the reaction mixture is cooled to room temperature and the aqueous layer is neutralized to pH˜7 by adding 1M aqueous HCl solution. The aqueous layer is extracted with ethyl acetate 3 times. The organic layers are combined, washed with brine, dried over Na2SO4 and filtered. The filtrate is concentrated under reduced pressure to yield the title compound. Yield: 94.2%. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.20 (6H, s), 3.38 (3H, s), 3.47 (2H, s), 3.50-3.55 (2H, m), 3.57-3.62 (2H, m), 3.80 (2H, s). After the addition at reflux for 3 h The aqueous layer is extracted with ethyl acetate 3 times washed with brine dried over Na2SO4 filtered The filtrate is concentrated under reduced pressure

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

実験手順: To a solution of methyl 3-hydroxy-2,2-dimethyl-propionate (2.72 mL, 21.28 mmol) in 3 mL of DMF is added 60% sodium hydride in mineral oil (1.70 g, 42.56 mmol) in one portion, followed by the addition of 2-bromoethyl methyl ether (4.0 mL, 42.56 mmol). The reaction mixture is stirred at room temperature for 3 hs. After this time, the reaction mixture is quenched with saturated aqueous NH4Cl solution and the product is extracted with DCM twice. The organics are combined and washed with water 4 times then brine, dried over Na2SO4, filtered and concentrated under reduced pressure to yield the title compound. Yield: 76%; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.19 (6H, s), 3.36 (3H, s), 3.48 (2H, s), 3.48-3.52 (2H, m), 3.54-3.60 (2H, m), 3.67 (3H, s). After this time, the reaction mixture is quenched with saturated aqueous NH4Cl solution the product is extracted with DCM twice washed with water 4 times brine, dried over Na2SO4 filtered concentrated under reduced pressure