1-O-tert-butyl 2-O-ethyl (2R)-2,3-dihydropyrrole-1,2-dicarboxylate

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

実験手順: To a solution of (R)-1-tert-butyl 2-ethyl 5-oxopyrrolidine-1,2-dicarboxylate (D24) (14.3 g, 55.58 mmol) in toluene (100 ml) cooled at −50° C., LiEt3BH 1M sol in THF (58.4 ml, 58.36 mmol) was added dropwise maintaining the reaction temperature below −45° C. After complete addition the mixture was stirred at −45° C. for 30 min. DIPEA (42 ml, 239 mmol), DMAP (102 mg, 0.83 mmol) and TFAA (8.9 ml, 63.92 mmol) were added sequentially maintaining the reaction temperature below −45° C. After complete addition, the reaction mixture was warmed to 20-25° C. within one hour and kept for an additional 2 hrs at this temperature. The reaction mixture was slowly charged with water (8 ml) so that the temperature did not exceed 5° C. and diluted with EtOAc (50 ml). Aqueous and organic phases were then separated and the organics washed again with water (8 ml), dried over Na2SO4 and evaporated to obtain residue which was purified by Biotage SNAP-Si cartridge (50 g) eluting with cHex/EtOAc from 90/10 to 50/50. Collected fractions, after solvent evaporation afforded the title compound (D25) (10.4 g). was added dropwise maintaining the reaction temperature below −45° C After complete addition the mixture maintaining the reaction temperature below −45° C After complete addition the reaction mixture was warmed to 20-25° C. within one hour kept for an additional 2 hrs at this temperature did not exceed 5° C. Aqueous and organic phases were then separated the organics washed again with water (8 ml) dried over Na2SO4 evaporated to obtain residue which was purified by Biotage SNAP-Si cartridge (50 g) eluting with cHex/EtOAc from 90/10 to 50/50 Collected fractions, after solvent evaporation

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

実験手順: To a solution of (R)-1-tert-butyl 2-ethyl 5-oxopyrrolidine-1,2-dicarboxylate (D24) (14.3 g, 55.58 mmol) in toluene (100 ml) cooled at −50° C., LiEt3BH 1M sol in THF (58.4 ml, 58.36 mmol) was added dropwise maintaining the reaction temperature below −45° C. After complete addition the mixture was stirred at −45° C. for 30 min. DIPEA (42 ml, 239 mmol), DMAP (102 mg, 0.83 mmol) and TFAA (8.9 ml, 63.92 mmol) were added sequentially maintaining the reaction temperature below −45° C. After complete addition, the reaction mixture was warmed to 20-25° C. within one hour and kept for an additional 2 hrs at this temperature. The reaction mixture was slowly charged with water (8 ml) so that the temperature did not exceed 5° C. and diluted with EtOAc (50 ml). Aqueous and organic phases were then separated and the organics washed again with water (8 ml), dried over Na2SO4 and evaporated to obtain residue which was purified by Biotage SNAP-Si cartridge (50 g) eluting with cHex/EtOAc from 90/10 to 50/50. Collected fractions, after solvent evaporation afforded the title compound (D25) (10.4 g). was added dropwise maintaining the reaction temperature below −45° C After complete addition the mixture maintaining the reaction temperature below −45° C After complete addition the reaction mixture was warmed to 20-25° C. within one hour kept for an additional 2 hrs at this temperature did not exceed 5° C. Aqueous and organic phases were then separated the organics washed again with water (8 ml) dried over Na2SO4 evaporated to obtain residue which was purified by Biotage SNAP-Si cartridge (50 g) eluting with cHex/EtOAc from 90/10 to 50/50 Collected fractions, after solvent evaporation