diethyl 2-methyl-2-(3-methylbutyl)propanedioate

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: A solution of 2-methyl-2-(3-methyl-butyl)-malonic acid diethyl ester (500 mg, 2.05 mmol) in anhydrous dichloromethane (4 mL) was stirred at −78° C. under a blanket of nitrogen and treated dropwise via syringe with a 1.0 M solution of diisobutylaluminum hydride in toluene (4.1 mL, 4.1 mmol) over a period of 15 min. The reaction was stirred for 4 h at −78° C. and quenched sequentially with a saturated aqueous ammonium chloride solution (3 mL) and a 4% aqueous hydrochloric acid solution (3 mL). The resulting gelatinous suspension was allowed to warm to 25° C. and was filtered through a sintered glass funnel. The filtrate was concentrated in vacuo. The resulting crude oil was purified by flash column chromatography (Teledyne Isco RediSep column; 0-20% ethyl acetate in hexanes) to afford the desired product, 2-formyl-2,5-dimethyl-hexanoic acid ethyl ester (150 mg, 0.75 mmol, 36%), as a clear oil. 1H NMR (400 MHz, CDCl3) δ: 0.89 (d, 6H, J=6.9 Hz), 1.07-1.15 (m, 2H), 1.23-1.26 (m, 3H), 1.28 (s, 3H), 1.52 (septet, 1H, J=6.6 Hz), 1.83-1.92 (m, 2H), 4.21 (q, 2H, J=6.9 Hz), 9.69 (s, 1H). quenched sequentially with a saturated aqueous ammonium chloride solution (3 mL) to warm to 25° C. was filtered through a sintered glass funnel The filtrate was concentrated in vacuo The resulting crude oil was purified by flash column chromatography (Teledyne Isco RediSep column; 0-20% ethyl acetate in hexanes)

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of diethyl isopentylmalonate (2.31 g, 10 mmol) in a 6:2 mixture of anhydrous N,N-dimethylformamide/diethyl ether (8 mL) was stirred under a nitrogen atmosphere at 25° C. and treated with a 60% oil dispersion of sodium hydride (480 mg, 12 mmol). The reaction mixture was stirred until the evolution of hydrogen gas ceased. The reaction was then treated dropwise via syringe with iodomethane (1.87 mL, 30 mmol) and stirred for 3 h at 25° C. The reaction was quenched with a 1.0 M aqueous hydrochloric acid solution (30 mL) and extracted with diethyl ether (2×50 mL). The combined organic layers were washed with a saturated aqueous sodium bicarbonate solution (50 mL) and saturated aqueous brine solution (50 mL), dried over sodium sulfate, filtered, and concentrated in vacuo to afford the desired product, 2-methyl-2-(3-methyl-butyl)-malonic acid diethyl ester (2.09 g, 8.56 mmol, 85%), as a clear oil. 1H NMR (400 MHz, CDCl3) δ: 0.88 (d, 6H, J=6.9 Hz), 1.06-1.12 (m, 2H), 1.24 (t, 6H, J=7.0 Hz), 1.38 (s, 3H), 1.51 (septet, 1H, J=6.6 Hz), 1.82-1.87 (m, 2H), 4.12-4.20 (m, 4H). LC-MS (ESI) calculated for C13H24O4 244.17. found 245.3 [M+H+]. stirred for 3 h at 25° C The reaction was quenched with a 1.0 M aqueous hydrochloric acid solution (30 mL) extracted with diethyl ether (2×50 mL) The combined organic layers were washed with a saturated aqueous sodium bicarbonate solution (50 mL) and saturated aqueous brine solution (50 mL) dried over sodium sulfate filtered concentrated in vacuo

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Diisobutylaluminum hydride (97.5 mL of a 1.0 M solution in toluene, 97.5 mmol) was added over 10 min to a solution of rac-2-methyl-2-(3-methyl-butyl)-malonic acid diethyl ester (11.91 g, 48.7 mmol) in dichloromethane (100 mL) at −78° C. The reaction mixture was stirred at that temperature for 4 h, and then was quenched with saturated aqueous ammonium chloride (100 mL). The cold bath was removed, 1.0 M aqueous hydrochloric acid solution (300 mL) and DL-tartaric acid (12 g) were added sequentially, and the mixture was allowed to warm to 25° C. over 2 h with vigorous stirring. The biphasic mixture was then partitioned between 1.0 M aqueous hydrochloric acid solution (150 mL) and dichloromethane (350 mL). The organic layer was dried over sodium sulfate and was concentrated in vacuo to afford the crude product, rac-2-formyl-2,5-dimethyl-hexanoic acid ethyl ester (8.80 g, 44 mmol, 90%). was quenched with saturated aqueous ammonium chloride (100 mL) The cold bath was removed 1.0 M aqueous hydrochloric acid solution (300 mL) and DL-tartaric acid (12 g) were added sequentially The biphasic mixture was then partitioned between 1.0 M aqueous hydrochloric acid solution (150 mL) and dichloromethane (350 mL) The organic layer was dried over sodium sulfate was concentrated in vacuo

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Palladium on carbon (4.26 g, 5%, “50% wet”, Alfa) was added to a solution of rac-2-methyl-2-(3-methyl-but-2-enyl)-malonic acid diethyl ester (12.15 g, 50.1 mmol) in ethyl acetate (225 mL) at 25° C. The atmosphere above the reaction mixture was evacuated and replaced with hydrogen from a balloon (3 cycles). The reaction mixture was then stirred under an atmosphere of hydrogen (3 balloons) at 25° C. for 21 h, and then was filtered through Celite. The filtrate was concentrated in vacuo to afford rac-2-methyl-2-(3-methyl-butyl)-malonic acid diethyl ester (11.91 g, 48.7 mmol, 98%) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ: 0.89 (6H, d, J=7.0 Hz), 1.07-1.13 (2H, m), 1.25 (6H, t, J=6.9 Hz), 1.39 (1H, s), 1.48-1.57 (1H, m), 1.84-1.88 (1H, m), 4.13-4.21 (2H, m). The atmosphere above the reaction mixture was evacuated was filtered through Celite The filtrate was concentrated in vacuo

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

実験手順: A solution of 2-methyl-2-(3-methyl-butyl)-malonic acid diethyl ester (500 mg, 2.05 mmol) in anhydrous dichloromethane (4 mL) was stirred at −78° C. under a blanket of nitrogen and treated dropwise via syringe with a 1.0 M solution of diisobutylaluminum hydride in toluene (4.1 mL, 4.1 mmol) over a period of 15 min. The reaction was stirred for 4 h at −78° C. and quenched sequentially with a saturated aqueous ammonium chloride solution (3 mL) and a 4% aqueous hydrochloric acid solution (3 mL). The resulting gelatinous suspension was allowed to warm to 25° C. and was filtered through a sintered glass funnel. The filtrate was concentrated in vacuo. The resulting crude oil was purified by flash column chromatography (Teledyne Isco RediSep column; 0-20% ethyl acetate in hexanes) to afford the desired product, 2-formyl-2,5-dimethyl-hexanoic acid ethyl ester (150 mg, 0.75 mmol, 36%), as a clear oil. 1H NMR (400 MHz, CDCl3) δ: 0.89 (d, 6H, J=6.9 Hz), 1.07-1.15 (m, 2H), 1.23-1.26 (m, 3H), 1.28 (s, 3H), 1.52 (septet, 1H, J=6.6 Hz), 1.83-1.92 (m, 2H), 4.21 (q, 2H, J=6.9 Hz), 9.69 (s, 1H). quenched sequentially with a saturated aqueous ammonium chloride solution (3 mL) to warm to 25° C. was filtered through a sintered glass funnel The filtrate was concentrated in vacuo The resulting crude oil was purified by flash column chromatography (Teledyne Isco RediSep column; 0-20% ethyl acetate in hexanes)

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of diethyl isopentylmalonate (2.31 g, 10 mmol) in a 6:2 mixture of anhydrous N,N-dimethylformamide/diethyl ether (8 mL) was stirred under a nitrogen atmosphere at 25° C. and treated with a 60% oil dispersion of sodium hydride (480 mg, 12 mmol). The reaction mixture was stirred until the evolution of hydrogen gas ceased. The reaction was then treated dropwise via syringe with iodomethane (1.87 mL, 30 mmol) and stirred for 3 h at 25° C. The reaction was quenched with a 1.0 M aqueous hydrochloric acid solution (30 mL) and extracted with diethyl ether (2×50 mL). The combined organic layers were washed with a saturated aqueous sodium bicarbonate solution (50 mL) and saturated aqueous brine solution (50 mL), dried over sodium sulfate, filtered, and concentrated in vacuo to afford the desired product, 2-methyl-2-(3-methyl-butyl)-malonic acid diethyl ester (2.09 g, 8.56 mmol, 85%), as a clear oil. 1H NMR (400 MHz, CDCl3) δ: 0.88 (d, 6H, J=6.9 Hz), 1.06-1.12 (m, 2H), 1.24 (t, 6H, J=7.0 Hz), 1.38 (s, 3H), 1.51 (septet, 1H, J=6.6 Hz), 1.82-1.87 (m, 2H), 4.12-4.20 (m, 4H). LC-MS (ESI) calculated for C13H24O4 244.17. found 245.3 [M+H+]. stirred for 3 h at 25° C The reaction was quenched with a 1.0 M aqueous hydrochloric acid solution (30 mL) extracted with diethyl ether (2×50 mL) The combined organic layers were washed with a saturated aqueous sodium bicarbonate solution (50 mL) and saturated aqueous brine solution (50 mL) dried over sodium sulfate filtered concentrated in vacuo

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Diisobutylaluminum hydride (97.5 mL of a 1.0 M solution in toluene, 97.5 mmol) was added over 10 min to a solution of rac-2-methyl-2-(3-methyl-butyl)-malonic acid diethyl ester (11.91 g, 48.7 mmol) in dichloromethane (100 mL) at −78° C. The reaction mixture was stirred at that temperature for 4 h, and then was quenched with saturated aqueous ammonium chloride (100 mL). The cold bath was removed, 1.0 M aqueous hydrochloric acid solution (300 mL) and DL-tartaric acid (12 g) were added sequentially, and the mixture was allowed to warm to 25° C. over 2 h with vigorous stirring. The biphasic mixture was then partitioned between 1.0 M aqueous hydrochloric acid solution (150 mL) and dichloromethane (350 mL). The organic layer was dried over sodium sulfate and was concentrated in vacuo to afford the crude product, rac-2-formyl-2,5-dimethyl-hexanoic acid ethyl ester (8.80 g, 44 mmol, 90%). was quenched with saturated aqueous ammonium chloride (100 mL) The cold bath was removed 1.0 M aqueous hydrochloric acid solution (300 mL) and DL-tartaric acid (12 g) were added sequentially The biphasic mixture was then partitioned between 1.0 M aqueous hydrochloric acid solution (150 mL) and dichloromethane (350 mL) The organic layer was dried over sodium sulfate was concentrated in vacuo

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Palladium on carbon (4.26 g, 5%, “50% wet”, Alfa) was added to a solution of rac-2-methyl-2-(3-methyl-but-2-enyl)-malonic acid diethyl ester (12.15 g, 50.1 mmol) in ethyl acetate (225 mL) at 25° C. The atmosphere above the reaction mixture was evacuated and replaced with hydrogen from a balloon (3 cycles). The reaction mixture was then stirred under an atmosphere of hydrogen (3 balloons) at 25° C. for 21 h, and then was filtered through Celite. The filtrate was concentrated in vacuo to afford rac-2-methyl-2-(3-methyl-butyl)-malonic acid diethyl ester (11.91 g, 48.7 mmol, 98%) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ: 0.89 (6H, d, J=7.0 Hz), 1.07-1.13 (2H, m), 1.25 (6H, t, J=6.9 Hz), 1.39 (1H, s), 1.48-1.57 (1H, m), 1.84-1.88 (1H, m), 4.13-4.21 (2H, m). The atmosphere above the reaction mixture was evacuated was filtered through Celite The filtrate was concentrated in vacuo

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Palladium on carbon (4.26 g, 5%, “50% wet”, Alfa) was added to a solution of rac-2-methyl-2-(3-methyl-but-2-enyl)-malonic acid diethyl ester (12.15 g, 50.1 mmol) in ethyl acetate (225 mL) at 25° C. The atmosphere above the reaction mixture was evacuated and replaced with hydrogen from a balloon (3 cycles). The reaction mixture was then stirred under an atmosphere of hydrogen (3 balloons) at 25° C. for 21 h, and then was filtered through Celite. The filtrate was concentrated in vacuo to afford rac-2-methyl-2-(3-methyl-butyl)-malonic acid diethyl ester (11.91 g, 48.7 mmol, 98%) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ: 0.89 (6H, d, J=7.0 Hz), 1.07-1.13 (2H, m), 1.25 (6H, t, J=6.9 Hz), 1.39 (1H, s), 1.48-1.57 (1H, m), 1.84-1.88 (1H, m), 4.13-4.21 (2H, m). The atmosphere above the reaction mixture was evacuated was filtered through Celite The filtrate was concentrated in vacuo

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

実験手順: A solution of 2-methyl-2-(3-methyl-butyl)-malonic acid diethyl ester (500 mg, 2.05 mmol) in anhydrous dichloromethane (4 mL) was stirred at −78° C. under a blanket of nitrogen and treated dropwise via syringe with a 1.0 M solution of diisobutylaluminum hydride in toluene (4.1 mL, 4.1 mmol) over a period of 15 min. The reaction was stirred for 4 h at −78° C. and quenched sequentially with a saturated aqueous ammonium chloride solution (3 mL) and a 4% aqueous hydrochloric acid solution (3 mL). The resulting gelatinous suspension was allowed to warm to 25° C. and was filtered through a sintered glass funnel. The filtrate was concentrated in vacuo. The resulting crude oil was purified by flash column chromatography (Teledyne Isco RediSep column; 0-20% ethyl acetate in hexanes) to afford the desired product, 2-formyl-2,5-dimethyl-hexanoic acid ethyl ester (150 mg, 0.75 mmol, 36%), as a clear oil. 1H NMR (400 MHz, CDCl3) δ: 0.89 (d, 6H, J=6.9 Hz), 1.07-1.15 (m, 2H), 1.23-1.26 (m, 3H), 1.28 (s, 3H), 1.52 (septet, 1H, J=6.6 Hz), 1.83-1.92 (m, 2H), 4.21 (q, 2H, J=6.9 Hz), 9.69 (s, 1H). quenched sequentially with a saturated aqueous ammonium chloride solution (3 mL) to warm to 25° C. was filtered through a sintered glass funnel The filtrate was concentrated in vacuo The resulting crude oil was purified by flash column chromatography (Teledyne Isco RediSep column; 0-20% ethyl acetate in hexanes)

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of diethyl isopentylmalonate (2.31 g, 10 mmol) in a 6:2 mixture of anhydrous N,N-dimethylformamide/diethyl ether (8 mL) was stirred under a nitrogen atmosphere at 25° C. and treated with a 60% oil dispersion of sodium hydride (480 mg, 12 mmol). The reaction mixture was stirred until the evolution of hydrogen gas ceased. The reaction was then treated dropwise via syringe with iodomethane (1.87 mL, 30 mmol) and stirred for 3 h at 25° C. The reaction was quenched with a 1.0 M aqueous hydrochloric acid solution (30 mL) and extracted with diethyl ether (2×50 mL). The combined organic layers were washed with a saturated aqueous sodium bicarbonate solution (50 mL) and saturated aqueous brine solution (50 mL), dried over sodium sulfate, filtered, and concentrated in vacuo to afford the desired product, 2-methyl-2-(3-methyl-butyl)-malonic acid diethyl ester (2.09 g, 8.56 mmol, 85%), as a clear oil. 1H NMR (400 MHz, CDCl3) δ: 0.88 (d, 6H, J=6.9 Hz), 1.06-1.12 (m, 2H), 1.24 (t, 6H, J=7.0 Hz), 1.38 (s, 3H), 1.51 (septet, 1H, J=6.6 Hz), 1.82-1.87 (m, 2H), 4.12-4.20 (m, 4H). LC-MS (ESI) calculated for C13H24O4 244.17. found 245.3 [M+H+]. stirred for 3 h at 25° C The reaction was quenched with a 1.0 M aqueous hydrochloric acid solution (30 mL) extracted with diethyl ether (2×50 mL) The combined organic layers were washed with a saturated aqueous sodium bicarbonate solution (50 mL) and saturated aqueous brine solution (50 mL) dried over sodium sulfate filtered concentrated in vacuo