(2S,3S)-2-甲基吡咯烷-3-醇

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

实验步骤: Using 2,3-dichloro-4-fluorobenzonitrile (400.5 mg), 0.9 mol/L solution (2.35 mL) of (2S,3S)-2-methylpyrrolidin-3-ol in dimethyl sulfoxide and lithium carbonate (78 mg), the title compound was obtained as yellow crystals (yield: 417 mg) by an operation similar to that in Example 3.

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

实验步骤: Using 2,3-dichloro-4-fluoro-5-methylbenzonitrile (1.02 g), 0.9 M-dimethyl sulfoxide solution (5.56 ml) of (2S,3S)-3-hydroxy-2-methylpyrrolidine and lithium carbonate (370 mg), the title compound was obtained as a colorless solid (yield: 53 mg) by an operation similar to that in Example 3.

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

实验步骤: Using 4-fluoro-2-(trifluoromethyl)benzonitrile (851 mg), (2S,3S)-3-hydroxy-2-methylpyrrolidine (5 mmol) and lithium carbonate (665 mg), the title compound was obtained as a colorless solid (yield: 630 mg) by an operation similar to that in Example 3.

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

实验步骤: Using 2-chloro-4-fluoro-3-ethylbenzonitrile (1.01 g), (2S,3S)-3-hydroxy-2-methylpyrrolidine (8.25 mmol) and lithium carbonate (813 mg), the title compound was obtained as a colorless solid (yield: 147 mg) by an operation similar to that in Example 3.

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution (25 mL) of 2-chloro-4-fluoro-5-methylbenzonitrile (848 mg) in dimethyl sulfoxide were added 0.9M-dimethyl sulfoxide solution (5.56 mL) of (2S,3S)-3-hydroxy-2-methylpyrrolidine and lithium carbonate (370 mg), and the mixture was stirred at 100° C. for 1 hr. Water was added and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (developing solvent: hexane-ethyl acetate) and crystallized from ethyl acetate-hexane to give the title compound as a colorless solid (yield: 374 mg). the mixture was extracted with ethyl acetate The extract was washed with saturated brine dried over anhydrous sodium sulfate concentrated under reduced pressure The residue was purified by silica gel column chromatography (developing solvent: hexane-ethyl acetate) crystallized from ethyl acetate-hexane

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of (2S,3S)-3-hydroxy-2-methylpyrrolidine, 2-chloro-4-fluoro-3-methylbenzonitrile (424 mg), lithium carbonate (370 mg) and DMSO (12.5 ml) was stirred at 100° C. for 2 hr. The reaction mixture was cooled and partitioned between water and ethyl acetate. The organic layer was washed with water, dried (sodium sulfate), and concentrated. The obtained residue was purified by silica gel column chromatography (ethyl acetate-hexane), and crystallized from ethyl acetate-hexane to give the title compound (114 mg) as crystals. The reaction mixture was cooled partitioned between water and ethyl acetate The organic layer was washed with water dried (sodium sulfate) concentrated The obtained residue was purified by silica gel column chromatography (ethyl acetate-hexane) crystallized from ethyl acetate-hexane

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

实验步骤: To a suspension of (4S,5S)-4-hydroxy-5-methylpyrrolidin-2-one (10.45 g) in dry THF (418 mL) was added dropwise Red-Al (104.9 g: 363 mmol: 70% toluene solution) under ice-cooling and a nitrogen stream. The mixture was stirred at room temperature for 20 min, and further refluxed for 3 hr. The reaction mixture was ice-cooled again, and sodium carbonate decahydrate (41.6 g) was added under a nitrogen stream. The mixture was stirred at room temperature overnight, insoluble materials were filtered through celite and washed with THF. The filtrate and washing were combined and concentrated under reduced pressure to give (2S,3S)-3-hydroxy-2-methylpyrrolidine. Without further purification, this compound was diluted with DMSO to give 0.9 mol/L-DMSO solution. A solution (170 mL) of (2S,3S)-3-hydroxy-2-methylpyrrolidine in 0.9 mol/L-DMSO was diluted with water (200 mL), sodium hydrogen carbonate (24.6 g) and benzyl chloroformate (15 mL) were added, and the mixture was stirred at room temperature for 18 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give the title compound as a pale-yellow oil (yield: 20.64 g, 84%). Without further purification this compound was diluted with DMSO to give 0.9 mol/L-DMSO solution were added the mixture was extracted with ethyl acetate The extract was washed with saturated brine dried over anhydrous sodium sulfate concentrated under reduced pressure

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

实验步骤: To a suspension of (4S,5S)-4-hydroxy-5-methylpyrrolidin-2-one (10.45 g) in dry THF (418 mL) was added dropwise Red-Al (104.9 g: 363 mmol: 70% toluene solution) under ice-cooling and a nitrogen stream. The mixture was stirred at room temperature for 20 min, and further refluxed for 3 hr. The reaction mixture was ice-cooled again, and sodium carbonate decahydrate (41.6 g) was added under a nitrogen stream. The mixture was stirred at room temperature overnight, insoluble materials were filtered through celite and washed with THF. The filtrate and washing were combined and concentrated under reduced pressure to give (2S,3S)-3-hydroxy-2-methylpyrrolidine. Without further purification, this compound was diluted with DMSO to give 0.9 mol/L-DMSO solution. A solution (170 mL) of (2S,3S)-3-hydroxy-2-methylpyrrolidine in 0.9 mol/L-DMSO was diluted with water (200 mL), sodium hydrogen carbonate (24.6 g) and benzyl chloroformate (15 mL) were added, and the mixture was stirred at room temperature for 18 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give the title compound as a pale-yellow oil (yield: 20.64 g, 84%). Without further purification this compound was diluted with DMSO to give 0.9 mol/L-DMSO solution were added the mixture was extracted with ethyl acetate The extract was washed with saturated brine dried over anhydrous sodium sulfate concentrated under reduced pressure