tert-butyl N-[(2S)-1-oxohexan-2-yl]carbamate

反応条件: temp:-45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mechanically stirred suspension of lithium aluminum hydride (5.00 g, 0.131 mol) in ether (250 mL) was cooled to -45° C. under nitrogen. A solution of the product from Step A (28.3 g, 0.103 mol) in ether (125 mL) was added, maintaining the temperature below -35° C. When the addition was complete, the reaction was warmed to 5° C., then recooled to -45° C. A solution of potassium hydrogen sulfate (27.3 g, 0.200 mol) in water was slowly added, maintaining the temperature below -5° C. After quenching, the reaction was stirred at room temperature for 1 h. The mixture was filtered through Celite, the ether evaporated, and the remainder partitioned between ethyl acetate and 2% potassium hydrogen sulfate. After washing with saturated brine, drying over magnesium sulfate and solvent removal, the title compound was obtained. maintaining the temperature below -35° C When the addition the reaction was warmed to 5° C. recooled to -45° C maintaining the temperature below -5° C After quenching The mixture was filtered through Celite the ether evaporated the remainder partitioned between ethyl acetate and 2% potassium hydrogen sulfate After washing with saturated brine drying over magnesium sulfate and solvent removal

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

実験手順: The title compound was prepared according to the procedure described in Example 39, Step C, except using o-toluidine (0.32 mL, 3.00 mmol), 2(S)-(tert-butoxycarbonylamino)hexanal (0.538, 2.50 mmol), sodium triacetoxyborohydride (0.795 g, 3.75 mmol) in dichloroethane (10 mL) The crude product was purified by column chromatography to yield the title compound. The title compound was prepared was purified by column chromatography

反応条件: temp:-45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mechanically stirred suspension of lithium aluminum hydride (5.00 g, 0.131 mol) in ether (250 mL) was cooled to -45° C. under nitrogen. A solution of the product from Step A (28.3 g, 0.103 mol) in ether (125 mL) was added, maintaining the temperature below -35° C. When the addition was complete, the reaction was warmed to 5° C., then recooled to -45° C. A solution of potassium hydrogen sulfate (27.3 g, 0.200 mol) in water was slowly added, maintaining the temperature below -5° C. After quenching, the reaction was stirred at room temperature for 1 h. The mixture was filtered through Celite, the ether evaporated, and the remainder partitioned between ethyl acetate and 2% potassium hydrogen sulfate. After washing with saturated brine, drying over magnesium sulfate and solvent removal, the title compound was obtained. maintaining the temperature below -35° C When the addition the reaction was warmed to 5° C. recooled to -45° C maintaining the temperature below -5° C After quenching The mixture was filtered through Celite the ether evaporated the remainder partitioned between ethyl acetate and 2% potassium hydrogen sulfate After washing with saturated brine drying over magnesium sulfate and solvent removal

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

実験手順: Under an argon gas stream, N-(tert-butoxycarbonyl)-(L)-leucine methyl ester (9.8 g, 40 mmol) as dissolved in toluene (70 ml), and cooled to -78° C. To the solution, while keeping the temperature at -60 to -70° C., was added gradually aluminum diisobutyl hydride (toluene 1.0 M solution, 52 ml). After stirring at -78° C. for 40 minutes, the cooling bath was removed, and methanol (2.1 ml) and 20% aqueous citric acid solution (30 ml) were added to the mixture, followed by extraction with ethyl acetate. The organic layer was washed with 20% aqueous citric acid solution, a saturated aqueous sodium bicarbonate solution, water and a saturated aqueous sodium chloride solution, successively. The organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure to give (S)-2-(tert-butoxycarbonylamino)-5-methylpentanal (8.5 g). at -60 to -70° C. the cooling bath was removed methanol (2.1 ml) and 20% aqueous citric acid solution (30 ml) were added to the mixture followed by extraction with ethyl acetate The organic layer was washed with 20% aqueous citric acid solution The organic layer was dried over anhydrous sodium sulfate the solvent was evaporated under reduced pressure

反応条件: temp:-45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mechanically stirred suspension of lithium aluminum hydride (5.00 g, 0.131 mol) in ether (250 mL) was cooled to -45° C. under nitrogen. A solution of the product from Step A (28.3 g, 0.103 mol) in ether (125 mL) was added, maintaining the temperature below -35° C. When the addition was complete, the reaction was warmed to 5° C., then recooled to -45° C. A solution of potassium hydrogen sulfate (27.3 g, 0.200 mol) in water was slowly added, maintaining the temperature below -5° C. After quenching, the reaction was stirred at room temperature for 1 h. The mixture was filtered through Celite, the ether evaporated, and the remainder partitioned between ethyl acetate and 2% potassium hydrogen sulfate. After washing with saturated brine, drying over magnesium sulfate and solvent removal, the title compound was obtained. maintaining the temperature below -35° C When the addition the reaction was warmed to 5° C. recooled to -45° C maintaining the temperature below -5° C After quenching The mixture was filtered through Celite the ether evaporated the remainder partitioned between ethyl acetate and 2% potassium hydrogen sulfate After washing with saturated brine drying over magnesium sulfate and solvent removal

反応条件: temp:-45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mechanically stirred suspension of lithium aluminum hydride (5.00 g, 0.131 mol) in ether (250 mL) was cooled to -45° C. under nitrogen. A solution of the product from Step A (28.3 g, 0.103 mol) in ether (125 mL) was added, maintaining the temperature below -35° C. When the addition was complete, the reaction was warmed to 5° C., then recooled to -45° C. A solution of potassium hydrogen sulfate (27.3 g, 0.200 mol) in water was slowly added, maintaining the temperature below -5° C. After quenching, the reaction was stirred at room temperature for 1 h. The mixture was filtered through Celite, the ether evaporated, and the remainder partitioned between ethyl acetate and 2% potassium hydrogen sulfate. After washing with saturated brine, drying over magnesium sulfate and solvent removal, the title compound was obtained. maintaining the temperature below -35° C When the addition the reaction was warmed to 5° C. recooled to -45° C maintaining the temperature below -5° C After quenching The mixture was filtered through Celite the ether evaporated the remainder partitioned between ethyl acetate and 2% potassium hydrogen sulfate After washing with saturated brine drying over magnesium sulfate and solvent removal

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

実験手順: To a stirred solution of tert-butyl (1S)-1-formylpentylcarbamate in toluene was added water (50 mL), acetone cyanohydrin (16.4 mL, 180.0 mmol), potassium cyanide (250 mg) and tetrabutylammonium iodide (300 mg). The mixture was stirred at ambient temperature for 20 h, and then the layers were separated. The organic layer was washed with water (5×60 mL), dried with magnesium sulfate and concentrated in vacuo to afford the title compound (26.7 g, 92%) as a thick oil. The 1H NMR spectrum showed an approximately equal mixture of diastereomers. 1H NMR (400 MHz, DMSO-d6): δ 6.91,6.83 (2d, J=8 Hz, J=9 Hz, 1H), 6.54, 6.47 (2d, J=7 Hz, J=6 Hz, 1H), 4.44, 4.17 (2t, J=5 Hz, J=8 Hz, 1H), 3.60-3.50 (m, 1H), 1.65-1.10 (m, 6H), 1.34 (s, 9H), 0.80 (t, J=6 Hz, 3H). the layers were separated The organic layer was washed with water (5×60 mL) dried with magnesium sulfate concentrated in vacuo

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

実験手順: To a stirred solution of bis (2-methoxyethoxy) aluminum hydride (54.0 mL, 65% by weight in toluene, 180.0 mmol) in toluene (100 mL) at −20° C. was added a solution of tert-butyl (1S)-1-{[methoxy(methyl)amino]carbonyl}pentylcarbamate (35.0 g, 120.0 mmol) in toluene (100 mL) over 30 min. After 2 h at −20° C., 3M sodium chloride (300 mL) was added dropwise, and the layers were separated. The toluene portion was washed with 1N hydrochloric acid (2×100 mL), 0.1N sodium hydroxide (2×50 mL), and brine (50 mL), dried over magnesium sulfate, and concentrated to 200 mL. The aldehyde was used immediately in solution. An aliquot of the solution was removed and concentrated, and the aldehyde was analyzed immediately. 1H NMR (400 MHz, DMSO-d6): δ 9.39 (s, 1H), 7.23 (d, J=7 Hz, 1H), 3.75 (m, 1H), 1.70-1.08 (m, 6H), 1.36 (s, 9H), 0.81 (t, J=6 Hz, 3H). the layers were separated The toluene portion was washed with 1N hydrochloric acid (2×100 mL), 0.1N sodium hydroxide (2×50 mL), and brine (50 mL) dried over magnesium sulfate concentrated to 200 mL An aliquot of the solution was removed concentrated

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

実験手順: To a stirred solution of bis (2-methoxyethoxy) aluminum hydride (54.0 mL, 65% by weight in toluene, 180.0 mmol) in toluene (100 mL) at −20° C. was added a solution of tert-butyl (1S)-1-{[methoxy(methyl)amino]carbonyl}pentylcarbamate (35.0 g, 120.0 mmol) in toluene (100 mL) over 30 min. After 2 h at −20° C., 3M sodium chloride (300 mL) was added dropwise, and the layers were separated. The toluene portion was washed with 1N hydrochloric acid (2×100 mL), 0.1N sodium hydroxide (2×50 mL), and brine (50 mL), dried over magnesium sulfate, and concentrated to 200 mL. The aldehyde was used immediately in solution. An aliquot of the solution was removed and concentrated, and the aldehyde was analyzed immediately. 1H NMR (400 MHz, DMSO-d6): δ 9.39 (s, 1H), 7.23 (d, J=7 Hz, 1H), 3.75 (m, 1H), 1.70-1.08 (m, 6H), 1.36 (s, 9H), 0.81 (t, J=6 Hz, 3H). the layers were separated The toluene portion was washed with 1N hydrochloric acid (2×100 mL), 0.1N sodium hydroxide (2×50 mL), and brine (50 mL) dried over magnesium sulfate concentrated to 200 mL An aliquot of the solution was removed concentrated

反応条件: temp:-45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mechanically stirred suspension of lithium aluminum hydride (5.00 g, 0.131 mol) in ether (250 mL) was cooled to -45° C. under nitrogen. A solution of the product from Step A (28.3 g, 0.103 mol) in ether (125 mL) was added, maintaining the temperature below -35° C. When the addition was complete, the reaction was warmed to 5° C., then recooled to -45° C. A solution of potassium hydrogen sulfate (27.3 g, 0.200 mol) in water was slowly added, maintaining the temperature below -5° C. After quenching, the reaction was stirred at room temperature for 1 h. The mixture was filtered through Celite, the ether evaporated, and the remainder partitioned between ethyl acetate and 2% potassium hydrogen sulfate. After washing with saturated brine, drying over magnesium sulfate and solvent removal, the title compound was obtained. maintaining the temperature below -35° C When the addition the reaction was warmed to 5° C. recooled to -45° C maintaining the temperature below -5° C After quenching The mixture was filtered through Celite the ether evaporated the remainder partitioned between ethyl acetate and 2% potassium hydrogen sulfate After washing with saturated brine drying over magnesium sulfate and solvent removal

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

実験手順: The title compound was prepared according to the procedure described in Example 39, Step C, except using o-toluidine (0.32 mL, 3.00 mmol), 2(S)-(tert-butoxycarbonylamino)hexanal (0.538, 2.50 mmol), sodium triacetoxyborohydride (0.795 g, 3.75 mmol) in dichloroethane (10 mL) The crude product was purified by column chromatography to yield the title compound. The title compound was prepared 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: The title compound was prepared according to the procedure described in Example 39, Step C, except using o-toluidine (0.32 mL, 3.00 mmol), 2(S)-(tert-butoxycarbonylamino)hexanal (0.538, 2.50 mmol), sodium triacetoxyborohydride (0.795 g, 3.75 mmol) in dichloroethane (10 mL) The crude product was purified by column chromatography to yield the title compound. The title compound was prepared was purified by column chromatography