反应详情

A mixture of (±)-(4R*,5R*)-5-[(1S*)-hydroxy(5-phenyl(2-thienyl))methyl]-4-(4-aminophenyl)-1-methylpyrrolidin-2-one (Example 17, 105 mg, 0.30 mmol), paraformaldehyde (13 mg, 0.42 mmol) and sodium methoxide (81 mg, 1.5 mmol) in methanol (1 mL) was stirred overnight. After adding sodium borohydride (12 mg, 0.30 mmol) the reaction mixture was heated at the reflux temperature for 1 h, then treated with a 1M NaOH solution (1 mL). The resulting mixture was stirred for 10 min, diluted with water (10 mL) and extracted with EtOAc (2×10 mL). The organic layer was washed with a saturated NaCl solution, dried (Na2SO4) and concentrated under reduced pressure to give a yellow solid. The crude product was sequentially triturated with EtOAc, Et2O and hexane to provide (±)-(4R*,5R*)-5-[(1S*)-hydroxy(5-phenyl(2-thienyl))methyl]methyl-4-[4-(methylamino)phenyl]pyrrolidin-2-one (89 mg, 76%) as a white solid: TLC (EtOAc) Rf 0.34; mp: 212° C.

1. temperaturewas heated at the reflux temperature for 1 h
2. stirringThe resulting mixture was stirred for 10 min
3. extractionextracted with EtOAc (2×10 mL)
4. washThe organic layer was washed with a saturated NaCl solution
5. dry with materialdried (Na2SO4)
6. concentrationconcentrated under reduced pressure
7. customto give a yellow solid
8. customThe crude product was sequentially triturated with EtOAc, Et2O and hexane