dimethyl 3-hydroxypentanedioate

反応条件: temp:20.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Tert-pentanol (200 ml) was saturated with anhydrous ammonia at ambient pressure. This was cooled to ambient temperature and to this CaLB-T1-AMD enzyme (1.25 g) and dimethyl 3-hydroxyglutarate (25.3 g) were added. The resulting mixture was gently stirred with a magnetic stirrer at ambient temperature (20-21° C.) for 18 h. The enzyme was removed by filtration and washed with tert-pentanol (25 ml). The clear filtrate (200 g) was concentrated under reduced pressure at a maximum temperature of +50° C. to light brown oil. The oil was again dissolved in tert-pentanol (90 ml) and placed in a mechanically stirred 500 ml vessel. To this MTBE (Methyl tert-butyl ether) was slowly added under seeding with methyl (S)-3-hydroxyglutaramate (10 mg). The crystal suspension was cooled in an ice-bath to +5° C. The reaction mass was filtered, washed with MTBE and dried to yield (S)-methyl-3-hydroxyglutaramate. were added The enzyme was removed by filtration washed with tert-pentanol (25 ml) The clear filtrate (200 g) was concentrated under reduced pressure at a maximum temperature of +50° C. The oil was again dissolved in tert-pentanol (90 ml) To this MTBE (Methyl tert-butyl ether) was slowly added The crystal suspension was cooled in an ice-bath to +5° C The reaction mass was filtered washed with MTBE dried

反応条件: temp:20.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Tert-pentanol (200 ml) was saturated with anhydrous ammonia at ambient pressure. This was cooled to ambient temperature and to this CaLB-T1-AMD enzyme (1.25 g) and dimethyl 3-hydroxyglutarate (25.3 g) were added. The resulting mixture was gently stirred with a magnetic stirrer at ambient temperature (20-21° C.) for 18 h. The enzyme was removed by filtration and washed with tert-pentanol (25 ml). The clear filtrate (200 g) was concentrated under reduced pressure at a maximum temperature of +50° C. to light brown oil. The oil was again dissolved in tert-pentanol (90 ml) and placed in a mechanically stirred 500 ml vessel. To this MTBE (Methyl tert-butyl ether) was slowly added under seeding with methyl (S)-3-hydroxyglutaramate (10 mg). The crystal suspension was cooled in an ice-bath to +5° C. The reaction mass was filtered, washed with MTBE and dried to yield (S)-methyl-3-hydroxyglutaramate. were added The enzyme was removed by filtration washed with tert-pentanol (25 ml) The clear filtrate (200 g) was concentrated under reduced pressure at a maximum temperature of +50° C. The oil was again dissolved in tert-pentanol (90 ml) To this MTBE (Methyl tert-butyl ether) was slowly added The crystal suspension was cooled in an ice-bath to +5° C The reaction mass was filtered washed with MTBE dried

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

実験手順: To a solution of dimethyl 3-hydroxypentanedioate (9 g, 51.1 mmol) in DMF (70 mL) was added Ag2O (35.5 g, 154.3 mmol) and iodomethane (48.2 g, 339.2 mmol) under ice-cooling. The mixture was stirred at room temperature overnight. The mixture was filtrated and the filtrate was washed with water. Ether was added and the organic layer was dried and concentrated to give the crude product, which was purified by column chromatography to give dimethyl 3-methoxypentanedioate (8 g, 82%). 1H-NMR (CDCl3): 2.48 (m, 4H), 3.21 (m, 3H), 3.50 (m, 6H), 3.85 (s, 1H). cooling The mixture was filtrated the filtrate was washed with water Ether was added the organic layer was dried concentrated to give the crude product, which was purified by column chromatography

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

実験手順: To a solution of dimethyl 3-hydroxypentanedioate (9 g, 51.1 mmol) in DMF (70 mL) was added Ag2O (35.5 g, 154.3 mmol) and iodomethane (48.2 g, 339.2 mmol) under ice-cooling. The mixture was stirred at room temperature overnight. The mixture was filtrated and the filtrate was washed with water. Ether was added and the organic layer was dried and concentrated to give the crude product, which was purified by column chromatography to give dimethyl 3-methoxypentanedioate (8 g, 82%). 1H-NMR (CDCl3): 2.48 (m, 4H), 3.21 (m, 3H), 3.50 (m, 6H), 3.85 (s, 1H). cooling The mixture was filtrated the filtrate was washed with water Ether was added the organic layer was dried concentrated to give the crude product, which was purified by column chromatography

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

実験手順: To a mixture of dimethyl 3-oxopentanedioate (20 g, 115 mmol) in anhydrous MeOH (140 mL) was added NaBH4 (2.33 g, 63.18 mmol) in small portions over 10 minutes. The mixture was stirred for 1 h at room temperature and concentrated. Water and EtOAc was added and the organic phase was separated and dried. The combined organic layer was concentrated to give the crude product, which was purified by column chromatography to give dimethyl 3-hydroxypentanedioate (9 g, 44%). 1H-NMR (CDCl3): 2.51 (m, 4H), 3.43 (m, 1H), 3.70 (m, 6H), 4.45 (m, 1H). concentrated Water and EtOAc was added the organic phase was separated dried The combined organic layer was concentrated to give the crude product, which was purified by column chromatography

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

実験手順: To a solution of dimethyl 3-hydroxypentanedioate (9 g, 51.1 mmol) in DMF (70 mL) was added Ag2O (35.5 g, 154.3 mmol) and iodomethane (48.2 g, 339.2 mmol) under ice-cooling. The mixture was stirred at room temperature overnight. The mixture was filtrated and the filtrate was washed with water. Ether was added and the organic layer was dried and concentrated to give the crude product, which was purified by column chromatography to give dimethyl 3-methoxypentanedioate (8 g, 82%). 1H-NMR (CDCl3): 2.48 (m, 4H), 3.21 (m, 3H), 3.50 (m, 6H), 3.85 (s, 1H). cooling The mixture was filtrated the filtrate was washed with water Ether was added the organic layer was dried concentrated to give the crude product, which was purified by column chromatography

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

実験手順: To a mixture of dimethyl 3-oxopentanedioate (20 g, 115 mmol) in anhydrous MeOH (140 mL) was added NaBH4 (2.33 g, 63.18 mmol) in small portions over 10 minutes. The mixture was stirred for 1 h at room temperature and concentrated. Water and EtOAc was added and the organic phase was separated and dried. The combined organic layer was concentrated to give the crude product, which was purified by column chromatography to give dimethyl 3-hydroxypentanedioate (9 g, 44%). 1H-NMR (CDCl3): 2.51 (m, 4H), 3.43 (m, 1H), 3.70 (m, 6H), 4.45 (m, 1H). concentrated Water and EtOAc was added the organic phase was separated dried The combined organic layer was concentrated to give the crude product, which was purified by column chromatography

反応条件: temp:20.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Tert-pentanol (200 ml) was saturated with anhydrous ammonia at ambient pressure. This was cooled to ambient temperature and to this CaLB-T1-AMD enzyme (1.25 g) and dimethyl 3-hydroxyglutarate (25.3 g) were added. The resulting mixture was gently stirred with a magnetic stirrer at ambient temperature (20-21° C.) for 18 h. The enzyme was removed by filtration and washed with tert-pentanol (25 ml). The clear filtrate (200 g) was concentrated under reduced pressure at a maximum temperature of +50° C. to light brown oil. The oil was again dissolved in tert-pentanol (90 ml) and placed in a mechanically stirred 500 ml vessel. To this MTBE (Methyl tert-butyl ether) was slowly added under seeding with methyl (S)-3-hydroxyglutaramate (10 mg). The crystal suspension was cooled in an ice-bath to +5° C. The reaction mass was filtered, washed with MTBE and dried to yield (S)-methyl-3-hydroxyglutaramate. were added The enzyme was removed by filtration washed with tert-pentanol (25 ml) The clear filtrate (200 g) was concentrated under reduced pressure at a maximum temperature of +50° C. The oil was again dissolved in tert-pentanol (90 ml) To this MTBE (Methyl tert-butyl ether) was slowly added The crystal suspension was cooled in an ice-bath to +5° C The reaction mass was filtered washed with MTBE dried

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

実験手順: To a solution of dimethyl 3-hydroxypentanedioate (9 g, 51.1 mmol) in DMF (70 mL) was added Ag2O (35.5 g, 154.3 mmol) and iodomethane (48.2 g, 339.2 mmol) under ice-cooling. The mixture was stirred at room temperature overnight. The mixture was filtrated and the filtrate was washed with water. Ether was added and the organic layer was dried and concentrated to give the crude product, which was purified by column chromatography to give dimethyl 3-methoxypentanedioate (8 g, 82%). 1H-NMR (CDCl3): 2.48 (m, 4H), 3.21 (m, 3H), 3.50 (m, 6H), 3.85 (s, 1H). cooling The mixture was filtrated the filtrate was washed with water Ether was added the organic layer was dried concentrated to give the crude product, which was purified by column chromatography

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

実験手順: To a mixture of dimethyl 3-oxopentanedioate (20 g, 115 mmol) in anhydrous MeOH (140 mL) was added NaBH4 (2.33 g, 63.18 mmol) in small portions over 10 minutes. The mixture was stirred for 1 h at room temperature and concentrated. Water and EtOAc was added and the organic phase was separated and dried. The combined organic layer was concentrated to give the crude product, which was purified by column chromatography to give dimethyl 3-hydroxypentanedioate (9 g, 44%). 1H-NMR (CDCl3): 2.51 (m, 4H), 3.43 (m, 1H), 3.70 (m, 6H), 4.45 (m, 1H). concentrated Water and EtOAc was added the organic phase was separated dried The combined organic layer was concentrated to give the crude product, which was purified by column chromatography