Reaction #1885059

Reaction equation

triflic anhydride

3-(4-chloro-3-methylphenyl)pyrrolidine

NaHCO3

DIEA

Morpholine

(R)-4-fluoro-N-(4-(3-hydroxy-2-oxopyrrolidin-1-yl)phenylsulfonyl]-N-(thiazol-2-yl)benzenesulfonamide

→

4-[(3′S)-3-(4-chloro-3-methylphenyl]-2′-oxo-1,3′-bipyrrolidin-1′-yl)-N-(thiazol-2-yl)benzenesulfonamide

Yield 74.0%

Solvents

DCM

DCM

DCM

Conditions

Workup

1. 1
   OtherSynthesized
2. 2
   workup.ADDITIONwas added dropwise over 5 minutes
3. 3
   workup.STIRRINGthe reaction mixture was stirred at −20° C. for 1.5 hours
4. 4
   workup.ADDITIONwas added
5. 5
   Otherthe phases were separated
6. 6
   ExtractionThe aqueous phase was extracted with DCM (5 mL)
7. 7
   Washwashed with saturated aqueous NaHCO3 (5×5 ml)
8. 8
   WashThe organic layer was washed with brine (5 mL)
9. 9
   Dryingdried over MgSO4
10. 10
    Otherabsorbed onto Celite
11. 11
    OtherPurification by silica gel column chromatography (1-5% MeOH in DCM)

Procedure

Synthesized according to General Procedure 9. To a stirred suspension of [(R)-4-fluoro-N-(4-(3-hydroxy-2-oxopyrrolidin-1-yl)phenylsulfonyl]-N-(thiazol-2-yl)benzenesulfonamide (500 mg, 1.01 mmol) in anhydrous DCM (10 mL) under nitrogen at −20° C. was added DIEA (0.88 mL, 5.03 mmol) followed by the dropwise addition of triflic anhydride (0.22 mL, 1.31 mmol) over 5 min. After stirring for 15 minutes at −20° C. a solution of 3-(4-chloro-3-methylphenyl)pyrrolidine (197 mg, 1.01 mmol) in anhydrous DCM (1 mL) was added dropwise over 5 minutes. The reaction mixture was continued to stir at −20° C. for 1 hour. Morpholine (0.35 mL, 4.02 mmol) was added and the reaction mixture was stirred at −20° C. for 1.5 hours. The reaction mixture was then poured into saturated aqueous NaHCO3 (10 mL), DCM (5 mL) was added and the phases were separated. The aqueous phase was extracted with DCM (5 mL). The organic portions were combined and washed with saturated aqueous NaHCO3 (5×5 ml). The organic layer was washed with brine (5 mL), dried over MgSO4 and absorbed onto Celite. Purification by silica gel column chromatography (1-5% MeOH in DCM) afforded 4-[(3′S)-3-(4-chloro-3-methylphenyl]-2′-oxo-1,3′-bipyrrolidin-1′-yl)-N-(thiazol-2-yl)benzenesulfonamide as a white solid (385 mg, 0.74 mmol, 74% yield). LC/MS (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)), m/z: M+1 obs=517.0; tR=1.11 min.

Source