(S)-1-BOC-2-(2-羟基乙基)吡咯烷

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: This compound was prepared from N-tert-butoxycarbonyl-L-β-homoprolinol [Leyendecker, F.; Jesser, F.; Laucher, D.; Tetrahedron Lett. 1983, 24, 3513-3516; 590 mg, 2.75 mmol] and 1-amino-6-hydroxy-isoquinoline (1e, 320 mg, 2.0 mmol) by the Mitsunobu procedure described in Example 1f. Yield: 650 mg (91%). ESI-MS: 358.0 (M+H)+. Rf (silica gel; dichloromethane/methanol, 9:1, v/v): 0.37.

反应条件: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Diisopropylethylamine (575 μl) was added to a solution of 2-[(2S)-1-tert-butoxycarbonylpyrrolidin-2-yl]acetic acid (688 mg) in tetrahydrofuran (15 ml, and the mixture was cooled to −20° C. Isobutyl chloroformate (428 μl) was added thereto, and the mixture was stirred at −20° C. for 45 minutes. The resulting solid was filtered off, and the solid was washed with tetrahydrofuran. Sodium borohydride (227 mg) was added to the filtrate, and the mixture was stirred at room temperature for 5 minutes. Then, methanol (5 ml) was added thereto, and the mixture was stirred at room temperature for 5 minutes. Ethyl acetate and water were added to the reaction solution to separate the aqueous and organic layers. The aqueous layer was subjected to extraction with ethyl acetate. The organic layers were combined, dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (n-hexane-ethyl acetate) to obtain tert-butyl (2S)-2-(2-hydroxyethyl)pyrrolidine-1-carboxylate (606 mg). The resulting solid was filtered off the solid was washed with tetrahydrofuran Sodium borohydride (227 mg) was added to the filtrate the mixture was stirred at room temperature for 5 minutes Then, methanol (5 ml) was added the mixture was stirred at room temperature for 5 minutes Ethyl acetate and water were added to the reaction solution to separate the aqueous and organic layers The aqueous layer was subjected to extraction with ethyl acetate dried over anhydrous sodium sulfate concentrated under reduced pressure The obtained residue was purified by silica gel column chromatography (n-hexane-ethyl acetate)

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 1-BOC-2-(S)-pyrrolidineethanal (6.80 g, 26.5 mmol) in anhydrous toluene (100 mL), cooled to -78° C. was added a 1M solution of diisobutylaluminum hydride in toluene (132.5 mL, 132.5 mmol). The reaction was stirred at -78° C. for 2 hours, and diisobutylaluminum hydride solution (26.50 mL, 26.5 mmol) was added. The mixture was stirred for 2 hours, then the reaction was quenched at -78° C. with methanol (150 mL). The mixture was poured into 1M Rochelle salt (500 mL), and the emulsified solution was extracted with ethyl acetate (200 mL). The organic layer was washed with brine, dried over MgSO4, and concentrated. The residue was purified on silica gel, eluting with methanol/methylene chloride (5:95) to yield a colorless oil (3.82 g, 67%). MS (DCI/NM) m/e: 216 (M+H)+. 1HNMR (CDCl3, 300 MHz) δ: 1.47 (s, 9H), 1.58-1.76 (m, 2H), 1.82-2.05 (m, 3H), 3.31 (t, J=6.0 Hz, 2H), 3.50-3.69 (m, 2H), 4.10-4.21 (m, 1H), 4.43 (dd, J=4.0, 7.0 Hz, 1H). The mixture was stirred for 2 hours the reaction was quenched at -78° C. with methanol (150 mL) The mixture was poured into 1M Rochelle salt (500 mL) the emulsified solution was extracted with ethyl acetate (200 mL) The organic layer was washed with brine dried over MgSO4 concentrated The residue was purified on silica gel eluting with methanol/methylene chloride (5:95)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: This compound was prepared from N-tert-butoxycarbonyl-L-β-homoprolinol [Leyendecker, F.; Jesser, F.; Laucher, D.; Tetrahedron Lett. 1983, 24, 3513-3516; 590 mg, 2.75 mmol] and 1-amino-6-hydroxy-isoquinoline (1e, 320 mg, 2.0 mmol) by the Mitsunobu procedure described in Example 1f. Yield: 650 mg (91%). ESI-MS: 358.0 (M+H)+. Rf (silica gel; dichloromethane/methanol, 9:1, v/v): 0.37.

反应条件: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Diisopropylethylamine (575 μl) was added to a solution of 2-[(2S)-1-tert-butoxycarbonylpyrrolidin-2-yl]acetic acid (688 mg) in tetrahydrofuran (15 ml, and the mixture was cooled to −20° C. Isobutyl chloroformate (428 μl) was added thereto, and the mixture was stirred at −20° C. for 45 minutes. The resulting solid was filtered off, and the solid was washed with tetrahydrofuran. Sodium borohydride (227 mg) was added to the filtrate, and the mixture was stirred at room temperature for 5 minutes. Then, methanol (5 ml) was added thereto, and the mixture was stirred at room temperature for 5 minutes. Ethyl acetate and water were added to the reaction solution to separate the aqueous and organic layers. The aqueous layer was subjected to extraction with ethyl acetate. The organic layers were combined, dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (n-hexane-ethyl acetate) to obtain tert-butyl (2S)-2-(2-hydroxyethyl)pyrrolidine-1-carboxylate (606 mg). The resulting solid was filtered off the solid was washed with tetrahydrofuran Sodium borohydride (227 mg) was added to the filtrate the mixture was stirred at room temperature for 5 minutes Then, methanol (5 ml) was added the mixture was stirred at room temperature for 5 minutes Ethyl acetate and water were added to the reaction solution to separate the aqueous and organic layers The aqueous layer was subjected to extraction with ethyl acetate dried over anhydrous sodium sulfate concentrated under reduced pressure The obtained residue was purified by silica gel column chromatography (n-hexane-ethyl acetate)