Reaction #2348668

Reaction equation

water

3-(3,5-dichlorophenyl)pyrrolidine

(R)-1-(3,5-difluorophenyl)-3-hydroxypyrrolidin-2-one

DIEA

→

(3′S)-3-(3,5-dichlorophenyl)-1′-(3,5-difluorophenyl)-1,3′-bipyrrolidin-2′-one

Solvents

DCM

DCM

Conditions

Workup

1. 1
   OtherSynthesized
2. 2
   workup.ADDITIONfollowed by the dropwise addition of triflic anyhydride (282 mg, 168 μL, 1.0 mmol)
3. 3
   workup.STIRRINGthe reaction mixture was stirred at −20° C. for 16 hours
4. 4
   Extractionextracted with EtOAc (3 ×)
5. 5
   WashThe combined organic phases were washed with brine
6. 6
   Dryingdried (Na2SO4)
7. 7
   Otherevaporated to dryness
8. 8
   OtherPurification by silica gel chromatography (0-20% EtOAC in DCM)

Procedure

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%).

Source