dimethyl 3-aminopentanedioate

反応条件: temp:0.00; pressure:0.00; stir:

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: Dimethyl 3-ketoglutarate (13 g) in methanol (50 ml) was treated with ammonium formate (5 g) and NaCNBH3 (2 g). 10 ml of H2O was added and the excess solvent removed under reduced pressure. The semi-solid was dissolved in 5% aqueous HCl (250 ml), and washed with CH2Cl2 (2×50 ml). The aqueous layer was made basic (pH>9) with K2CO3 and the product was extracted using CH2Cl2 (2×75 ml). The organic layers were combined and dried with Na2SO4. The excess solvent was removed to give 2.5 g of the dimethyl (±)3-aminoglutarate. This was dissolved in methanol (50 ml) and treated with 4N HCl/Dioxane (10 ml). The excess solvent was removed under reduced pressure to give a 2.7 g of dimethyl (±)3-aminoglutarate hydrochloride. MS and 1H-NMR were consistent with the desired product. the excess solvent removed under reduced pressure The semi-solid was dissolved in 5% aqueous HCl (250 ml) washed with CH2Cl2 (2×50 ml) the product was extracted dried with Na2SO4 The excess solvent was removed

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

実験手順: Dimethyl 3-ketoglutarate (13 g) in methanol (50 ml) was treated with ammonium formate (5 g) and NaCNBH3 (2 g). 10 ml of H2O was added and the excess solvent removed under reduced pressure. The semi-solid was dissolved in 5% aqueous HCl (250 ml), and washed with CH2Cl2 (2×50 ml). The aqueous layer was made basic (pH>9) with K2CO3 and the product was extracted using CH2Cl2 (2×75 ml). The organic layers were combined and dried with Na2SO4. The excess solvent was removed to give 2.5 g of the dimethyl (±)3-aminoglutarate. This was dissolved in methanol (50 ml) and treated with 4N HCl/Dioxane (10 ml). The excess solvent was removed under reduced pressure to give a 2.7 g of dimethyl (±)3-aminoglutarate hydrochloride. MS and 1H-NMR were consistent with the desired product. the excess solvent removed under reduced pressure The semi-solid was dissolved in 5% aqueous HCl (250 ml) washed with CH2Cl2 (2×50 ml) the product was extracted dried with Na2SO4 The excess solvent was removed

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

実験手順: Dimethyl-3-oxoglutarate (10 g, 57 mmol) was added to methanol (225 ml) followed by ammonium formate (36 g, 570 mmol) and NaBH3CN (3.7 g, 57 mmol) at 25° C. After 24 hours the methanol was removed in vacuo to leave a white mass. Methylene chloride was added and the mixture filtered. The methylene chloride was evaporated resulting in an oil which was dissolved in 1N HCl (200 ml) and extracted with ether (100 ml). The ether layer was discarded and the aqueous layer was made basic using solid K2CO3. The product was extracted into methylene chloride dried over Na2SO4 and evaporated to give dimethyl-3-aminoglutarate (7.5 g). 1H NMR (d6 -DMSO) δ1.76 (bs, 2H), 2.45 (dd, 4H, J=8.08 Hz, 16.64 Hz), 3.69 (s, 6H), 5.45 (m, 1H); MS (FAB) m/e 176.0 (M+H+). After 24 hours the methanol was removed in vacuo to leave a white mass the mixture filtered The methylene chloride was evaporated resulting in an oil which extracted with ether (100 ml) The product was extracted into methylene chloride dried over Na2SO4 evaporated

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: Dimethyl-3-oxoglutarate (10 g, 57 mmol) was added to methanol (225 ml) followed by ammonium formate (36 g, 570 mmol) and NaBH3CN (3.7 g, 57 mmol) at 25° C. After 24 hours the methanol was removed in vacuo to leave a white mass. Methylene chloride was added and the mixture filtered. The methylene chloride was evaporated resulting in an oil which was dissolved in 1N HCl (200 ml) and extracted with ether (100 ml). The ether layer was discarded and the aqueous layer was made basic using solid K2CO3. The product was extracted into methylene chloride dried over Na2SO4 and evaporated to give dimethyl-3-aminoglutarate (7.5 g). 1H NMR (d6 -DMSO) δ1.76 (bs, 2H), 2.45 (dd, 4H, J=8.08 Hz, 16.64 Hz), 3.69 (s, 6H), 5.45 (m, 1H); MS (FAB) m/e 176.0 (M+H+). After 24 hours the methanol was removed in vacuo to leave a white mass the mixture filtered The methylene chloride was evaporated resulting in an oil which extracted with ether (100 ml) The product was extracted into methylene chloride dried over Na2SO4 evaporated

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: Dimethyl-3-oxoglutarate (10 g, 57 mmol) was added to methanol (225 ml) followed by ammonium formate (36 g, 570 mmol) and NaBH3CN (3.7 g, 57 mmol) at 25° C. After 24 h, the methanol was removed in vacuo to leave a white mass. Methylene chloride was added and the mixture filtered. The methylene chloride was evaporated resulting in an oil which was dissolved in 1N HCl (200 ml) and extracted with ether (100 ml). The ether layer was discarded and the aqueous layer was made basic using solid K2CO3. The product was extracted into methylene chloride, dried over Na2SO4, and evaporated to give dimethyl-3-aminoglutarate (7.5 g). 1H NMR (d6-DMSO) δ 1.76 (bs, 2H), 2.45 (dd, 4H, J=8.1 Hz, 16.6 Hz), 3.69 (s, 6H), 5.45 (m, 1H); MS (FAB) m/z 176.0 (MH+). the methanol was removed in vacuo to leave a white mass the mixture filtered The methylene chloride was evaporated resulting in an oil which extracted with ether (100 ml) The product was extracted into methylene chloride dried over Na2SO4 evaporated

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

実験手順: Dimethyl-3-oxoglutarate (10 g, 57 mmol) was added to methanol (225 ml) followed by ammonium formate (36 g, 570 mmol) and NaBH3CN (3.7 g, 57 mmol) at 25° C. After 24 h, the methanol was removed in vacuo to leave a white mass. Methylene chloride was added and the mixture filtered. The methylene chloride was evaporated resulting in an oil which was dissolved in 1N HCl (200 ml) and extracted with ether (100 ml). The ether layer was discarded and the aqueous layer was made basic using solid K2CO3. The product was extracted into methylene chloride, dried over Na2SO4, and evaporated to give dimethyl-3-aminoglutarate (7.5 g). 1H NMR (d6-DMSO) δ 1.76 (bs, 2H), 2.45 (dd, 4H, J=8.1 Hz, 16.6 Hz), 3.69 (s, 6H), 5.45 (m, 1H); MS (FAB) m/z 176.0 (MH+). the methanol was removed in vacuo to leave a white mass the mixture filtered The methylene chloride was evaporated resulting in an oil which extracted with ether (100 ml) The product was extracted into methylene chloride dried over Na2SO4 evaporated

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

実験手順: Dimethyl-3-oxoglutarate (10 g, 57 mmol) was added to methanol (225 ml) followed by ammonium formate (36 g, 570 mmol) and NaBH3CN (3.7 g, 57 mmol) at 25° C. After 24 h, the methanol was removed in vacuo to leave a white mass. Methylene chloride was added and the mixture filtered. The methylene chloride was evaporated resulting in an oil which was dissolved in 1N HCl (200 ml) and extracted with ether (100 ml). The ether layer was discarded and the aqueous layer was made basic using solid K2CO3. The product was extracted into methylene chloride, dried over Na2SO4, and evaporated to give dimethyl-3-aminoglutarate (7.5 g). 1H NMR (d6-DMSO) δ 1.76 (bs, 2H), 2.45 (dd, 4H, J=8.1 Hz, 16.6 Hz), 3.69 (s, 6H), 5.45 (m, 1H); MS (FAB) m/z 176.0 (MH+). the methanol was removed in vacuo to leave a white mass the mixture filtered The methylene chloride was evaporated resulting in an oil which extracted with ether (100 ml) The product was extracted into methylene chloride dried over Na2SO4 evaporated

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

実験手順: A diluted alcoholic sulfuric acid solution is prepared by adding sulfuric acid (20.69 Kg) to i-PrOH (51.7 Kg) at 0-5° C. The resulting solution was slowly added to a solution of tert-butylamine borane (9.19 Kg) in THF (69.3 Kg), maintaining the temperature below −5° C. Dimethyl-3-aminoglutaconate (18.28 Kg) was slowly added to the resulting mixture, maintaining the temperature below 0° C. The resulting reaction mixture was stirred between 0° C. and 15° C. overnight, then quenched by slow addition to water (166 Kg) while maintaining the temperature below 10° C. and the pH between 5 and 7 by adding concentrated aqueous NaOH. The pH of the mixture was then adjusted to about 9-10 by adding concentrated aqueous NaOH at the end of the quenching process. The phases were separated and the aqueous phase was extracted with DCM. The combined organic extracts were washed with brine (20.6 Kg), filtered through a cotton cartridge and concentrated under reduced pressure to give 3-amino-pentanedioic acid dimethyl ester (17.87 Kg, 97% yield). maintaining the temperature below −5° C maintaining the temperature below 0° C The resulting reaction mixture quenched by slow addition to water (166 Kg) while maintaining the temperature below 10° C. the pH between 5 and 7 by adding concentrated aqueous NaOH by adding concentrated aqueous NaOH at the end of the quenching process The phases were separated the aqueous phase was extracted with DCM The combined organic extracts were washed with brine (20.6 Kg) filtered through a cotton cartridge concentrated under reduced pressure