Water → (3'S)-3-(3,5-dichlorophenyl)-1'-(3,5-difluorophenyl)-1,3'-bipyrrolidin-2'-one

Participants

Reaction Conditions

Reaction Steps

Synthesized according to General Procedure 10. To a solution of (R)-1-(3,5-difluorophenyl)-3-hydroxypyrrolidin-2-one (213 mg, 1.0 mmol) in DCM (0.7 mL) at −20° C. was added DIEA (259 mg, 348 μL, 2.0 mmol) followed by the dropwise addition of triflic anyhydride (282 mg, 168 μL, 1.0 mmol) and the reaction mixture was stirred at −20° C. for 45 min. A solution of 3-(3,5-dichlorophenyl)pyrrolidine (216 mg, 1.0 mmol) in DCM (0.7 mL) was added dropwise and the reaction mixture was stirred at −20° C. for 16 hours. The reaction mixture was poured into water and extracted with EtOAc (3×). The combined organic phases were washed with brine, dried (Na2SO4) and evaporated to dryness. Purification by silica gel chromatography (0-20% EtOAC in DCM) afforded (3′S)-3-(3,5-dichlorophenyl)-1′-(3,5-difluorophenyl)-1,3′-bipyrrolidin-2′-one as an oil that solidified upon standing (210 mg, 51%). 1H-NMR (400 MHz, CDCl3) 7.33-7.28 (m, 2H), 7.19-7.17 (m, 2H), 6.64-6.58 (m, 2H), 3.83-3.74 (m, 1H), 3.72 (dd, J=7.4, 8.7 Hz, 1H), 3.64-3.57 (m, 1H), 3.49-3.45 (m, 0.5H), 3.37-3.25 (m, 1.5H), 3.19 (m, 1H), 3.06-2.90 (m, 1.5H), 2.76 (dd, J=7.3, 9.0 Hz, 0.5H), 2.43-2.29 (m, 2H), 2.23-2.15 (m, 1H) and 1.94-1.85 (m, 1H) ppm. LC/MS (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)), m/z: M+1 obs=411.3; tR=1.46 min.

Provenance & Evidence