methyl 3-methyl-3-(phenylmethoxycarbonylamino)butanoate

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: A solution of 18.27 g (68.9 mmol) of 3-benzyloxycarbonylamino-3-methylbutanoic acid methyl ester in 20 mL of methanol at room temperature was treated dropwise with 51 mL of 2N NaOH (102 mmol). The mixture was stirred at room temperature for 16 hours then transferred to a separatory funnel and washed with hexane (3×). The aqueous layer was removed, cooled to 0° C. and slowly acidified to pH 2 (paper) by dropwise addition of 6N HCl. This mixture was extracted with ether (6×); combined extracts were washed with 1N HCl and brine, then dried over magnesium sulfate, filtered and solvent removed under vacuum to afford 17.26 g (68.7 mmol, 99%) of the product. 1H NMR (200 MHz, CDCl3): 1.42 (s, 6H), 2.77 (s, 2H), 5.06 (s, 2H), 5.2 (br s, 1H), 7.3 (s, 5H). then transferred to a separatory funnel washed with hexane (3×) The aqueous layer was removed cooled to 0° C. slowly acidified to pH 2 (paper) by dropwise addition of 6N HCl This mixture was extracted with ether (6×) combined extracts were washed with 1N HCl and brine dried over magnesium sulfate filtered solvent removed under vacuum

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

実験手順: To 14.7 g (91.8 mmol) of 2,2-dimethylbutanedioic acid-4-methyl ester in 150 mL of benzene was added 13 mL of triethylamine (9.4 g, 93 mmol) followed by 21.8 mL of diphenylphosphoryl azide (27.8 g, 101 mmol). The mixture was heated under nitrogen at reflux for 45 minutes, then 19 mL (19.9 g, 184 mmol) of benzyl alcohol was added and refluxing continued for 16 hours. The mixtue was cooled, filtered and the filtrate concentrated to a minimum volume under vacuum. The residue was redissolved in 250 mL of ethyl acetate, washed with water, saturated aqueous sodium bicarbonate (2×) and brine. The organic layer was removed, dried over magnesium sulfate, filtered and the filtrate concentrated to a minimum volume under vacuum. The crude product was purified by medium pressure liquid chromatography on silica, eluting with hexane/ethyl acetate (4:1), to afford 18.27 g (68.9 mmol, 75%) of the product. 1H NMR (200 MHz, CDCl3): 1.40 (s, 6H), 2.69 (s, 2H), 3.63 (s, 3H), 5.05 (s, 2H), 5.22 (br s, 1H), 7.32 (s, 5H). The mixture was heated under nitrogen at reflux for 45 minutes refluxing The mixtue was cooled filtered the filtrate concentrated to a minimum volume under vacuum The residue was redissolved in 250 mL of ethyl acetate washed with water, saturated aqueous sodium bicarbonate (2×) and brine The organic layer was removed dried over magnesium sulfate filtered the filtrate concentrated to a minimum volume under vacuum The crude product was purified by medium pressure liquid chromatography on silica eluting with hexane/ethyl acetate (4:1)

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

実験手順: A solution of 18.27 g (68.9 mmol) of methyl 3-benzyloxycarbonylamino-3-methylbutanoate (Step D) in 20 mL of methanol at room temperature was treated dropwise wit 51 mL of 2N NaOH (102 mmol, 1.5 eq). The mixture was stirred at room temperature for 16 hours then transferred to a separatory funnel and washed with hexane (3×). The aqueous layer was removed, cooled to 0° and slowly acidified to pH 2 (paper) by dropwise addition of 6N HCl. This mixture was extracted with ether (6×); combined extracts were washed with 1N HCl and brine, then dried over magnesium sulfate, filtered and solvent removed under vacuum to afford 17.26 g (68.7 mmol, 99%) of the product. 1H NMR (200 MHz,CDCl3): 1.42 (s,6 H), 2.77 (s,2 H), 5.06 (s,2 H), 5.2 (br s,1 H), 7.3 (s,5 H). then transferred to a separatory funnel washed with hexane (3×) The aqueous layer was removed cooled to 0° slowly acidified to pH 2 (paper) by dropwise addition of 6N HCl This mixture was extracted with ether (6×) combined extracts were washed with 1N HCl and brine dried over magnesium sulfate filtered solvent removed under vacuum

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

実験手順: A solution of 18.27 g (68.9 mmol) of 3-benzyloxycarbonylamino-3-methylbutanoic acid methyl ester in 20 mL of methanol at room temperature was treated dropwise with 51 mL of 2N NaOH (102 mmol). The mixture was stirred at room temperature for 16 hours then transferred to a separatory funnel and washed with hexane (3×). The aqueous layer was removed, cooled to 0° C. and slowly acidified to pH 2 (paper) by dropwise addition of 6N HCl. This mixture was extracted with ether (6×); combined extracts were washed with 1N HCl and brine, then dried over magnesium sulfate, filtered and solvent removed under vacuum to afford 17.26 g (68.7 mmol, 99%) of the product. then transferred to a separatory funnel washed with hexane (3×) The aqueous layer was removed cooled to 0° C. slowly acidified to pH 2 (paper) by dropwise addition of 6N HCl This mixture was extracted with ether (6×) combined extracts were washed with 1N HCl and brine dried over magnesium sulfate filtered solvent removed under vacuum

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

実験手順: To 14.7 g (91.8 mmol) of 2,2-dimethylbutanedioic acid-4-methyl ester in 150 mL of benzene was added 13 mL of triethylamine (9.4 g, 93 mmol) followed by 21.8 mL of diphenylphosphoryl azide (27.8 g, 101 mmol). The mixture was heated under nitrogen at reflux for 45 minutes then 19 mL (19.9 g, 184 mmol) of benzyl alcohol was added and refluxing continued for 16 hours. The mixture was cooled, filtered and the filtrate concentrated to a minimum volume under vacuum. The residue was redissolved in 250 mL of ethyl acetate, washed with water, saturated aqueous sodium bicarbonate (2×) and brine. The organic layer was removed, dried over magnesium sulfate, filtered and the filtrate concentrated to a minimum volume under vacuum. The crude product was purified by medium pressure liquid chromatography on silica, eluting with hexane/ethyl acetate (4:1), to afford 18.27 g (68.9 mmol, 75%) of the product. The mixture was heated under nitrogen at reflux for 45 minutes refluxing The mixture was cooled filtered the filtrate concentrated to a minimum volume under vacuum The residue was redissolved in 250 mL of ethyl acetate washed with water, saturated aqueous sodium bicarbonate (2×) and brine The organic layer was removed dried over magnesium sulfate filtered the filtrate concentrated to a minimum volume under vacuum The crude product was purified by medium pressure liquid chromatography on silica eluting with hexane/ethyl acetate (4:1)

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: A solution of 18.27 g (68.9 mmol) of 3-benzyloxycarbonylamino-3-methylbutanoic acid methyl ester in 20 mL of methanol at room temperature was treated dropwise with 51 mL of 2N NaOH (102 mmol). The mixture was stirred at room temperature for 16 hours then transferred to a separatory funnel and washed with hexane (3×). The aqueous layer was removed, cooled to 0° C. and slowly acidified to pH 2 (paper) by dropwise addition of 6N HCl. This mixture was extracted with ether (6×); combined extracts were washed with 1N HCl and brine, then dried over magnesium sulfate, filtered and solvent removed under vacuum to afford 17.26 g (68.7 mmol, 99%) of the product. then transferred to a separatory funnel washed with hexane (3×) The aqueous layer was removed cooled to 0° C. slowly acidified to pH 2 (paper) by dropwise addition of 6N HCl This mixture was extracted with ether (6×) combined extracts were washed with 1N HCl and brine dried over magnesium sulfate filtered solvent removed under vacuum

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

実験手順: To 14.7 g (91.8 mmol) of 2,2-dimethylbutanedioic acid-4-methyl ester in 150 mL of benzene was added 13 mL of triethylamine (9.4 g, 93 mmol) followed by 21.8 mL of diphenylphosphoryl azide (27.8 g, 101 mmol). The mixture was heated under nitrogen at reflux for 45 minutes then 19 mL (19.9 g, 184 mmol) of benzyl alcohol was added and refluxing continued for 16 hours. The mixture was cooled, filtered and the filtrate concentrated to a minimum volume under vacuum. The residue was redissolved in 250 mL of ethyl acetate, washed with water, saturated aqueous sodium bicarbonate (2×) and brine. The organic layer was removed, dried over magnesium sulfate, filtered and the filtrate concentrated to a minimum volume under vacuum. The crude product was purified by medium pressure liquid chromatography on silica, eluting with hexane/ethyl acetate (4:1), to afford 18.27 g (68.9 mmol, 75%) of the product. The mixture was heated under nitrogen at reflux for 45 minutes refluxing The mixture was cooled filtered the filtrate concentrated to a minimum volume under vacuum The residue was redissolved in 250 mL of ethyl acetate washed with water, saturated aqueous sodium bicarbonate (2×) and brine The organic layer was removed dried over magnesium sulfate filtered the filtrate concentrated to a minimum volume under vacuum The crude product was purified by medium pressure liquid chromatography on silica eluting with hexane/ethyl acetate (4:1)

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

実験手順: A solution of 18.3 g (68.9 mmol) of methyl 3-benzyloxycarbonylamino-3-methylbutanoate (Step B) in 20 mL of methanol at room temperature was treated dropwise with 51 mL of 2N NaOH (102 mmol, 1.5 eq). The mixture was stirred at room temperature for 16 hours then transferred to a separatory funnel and washed with hexane (3×). The aqueous layer was removed, cooled to 0° and slowly acidified to pH 2 (paper) by dropwise addition of 6N HCl. This mixture was extracted with ether (6×); combined extracts were washed with 1N HCl and brine, then dried over magnesium sulfate, filtered and solvent removed under vacuum to afford 17.3 g (68.7 mmol, 99%) of the product. 1H NMR (200 MHz, CDCl3): δ 1.42 (s, 6H), 2.77 (s, 2H), 5.06 (s, 2H), 5.2 (br s, 1H), 7.3 (s, 5H). then transferred to a separatory funnel washed with hexane (3×) The aqueous layer was removed cooled to 0° slowly acidified to pH 2 (paper) by dropwise addition of 6N HCl This mixture was extracted with ether (6×) combined extracts were washed with 1N HCl and brine dried over magnesium sulfate filtered solvent removed under vacuum

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

実験手順: A solution of 18.27 g (68.9 mmol) of 3-benzyloxycarbonylamino-3-methylbutanoic acid methyl ester in 20 mL of methanol at room temperature was treated dropwise with 51 mL of 2N NaOH (102 mmol). The mixture was stirred at room temperature for 16 hours then transferred to a separatory funnel and washed with hexane (3×). The aqueous layer was removed, cooled to 0° C. and slowly acidified to pH 2 (paper) by dropwise addition of 6N HCl. This mixture was extracted with ether (6×); combined extracts were washed with 1N HCl and brine, then dried over magnesium sulfate, filtered and solvent removed under vacuum to afford 17.26 g (68.7 mmol, 99%) of the product. then transferred to a separatory funnel washed with hexane (3×) The aqueous layer was removed cooled to 0° C. slowly acidified to pH 2 (paper) by dropwise addition of 6N HCl This mixture was extracted with ether (6×) combined extracts were washed with 1N HCl and brine dried over magnesium sulfate filtered solvent removed under vacuum

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

実験手順: To 14.7 g (91.8 mmol) of 2,2-dimethylbutanedioic acid-4-methyl ester in 150 mL of benzene was added 13 mL of triethylamine (9.4 g, 93 mmol) followed by 21.8 mL of diphenylphosphoryl azide (27.8 g, 101 mmol). The mixture was heated under nitrogen at reflux for 45 minutes then 19 mL (19.9 g, 184 mmol) of benzyl alcohol was added and refluxing continued for 16 hours. The mixture was cooled, filtered and the filtrate concentrated to a minimum volume under vacuum. The residue was redissolved in 250 mL of ethyl acetate, washed with water, saturated aqueous sodium bicarbonate (2×) and brine. The organic layer was removed, dried over magnesium sulfate, filtered and the filtrate concentrated to a minimum volume under vacuum. The crude product was purified by medium pressure liquid chromatography on silica, eluting with hexane/ethyl acetate (4:1), to afford 18.27 g (68.9 mmol, 75%) of the product. The mixture was heated under nitrogen at reflux for 45 minutes refluxing The mixture was cooled filtered the filtrate concentrated to a minimum volume under vacuum The residue was redissolved in 250 mL of ethyl acetate washed with water, saturated aqueous sodium bicarbonate (2×) and brine The organic layer was removed dried over magnesium sulfate filtered the filtrate concentrated to a minimum volume under vacuum The crude product was purified by medium pressure liquid chromatography on silica eluting with hexane/ethyl acetate (4:1)