Water → 4-[(3'S)-3-(3,5-Dichlorophenyl)-2'-oxo-1,3'-bipyrrolidin-1'-yl]-2,6-difluorobenzene-1-sulfonyl chloride

HRID 1098685Notes

Reaction equation

HRID 1098685 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]2[CH2:13][CH2:12][N:11]([C@H:14]3[CH2:18][CH2:17][N:16]([C:19]4[CH:24]=[C:23]([F:25])[CH:22]=[C:21]([F:26])[CH:20]=4)[C:15]3=[O:27])[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.[Cl:28][S:29](O)(=[O:31])=[O:30].O>ClCCCl>[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]2[CH2:13][CH2:12][N:11]([C@H:14]3[CH2:18][CH2:17][N:16]([C:19]4[CH:24]=[C:23]([F:25])[C:22]([S:29]([Cl:28])(=[O:31])=[O:30])=[C:21]([F:26])[CH:20]=4)[C:15]3=[O:27])[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1

Participants

5

Reactant 3

HCID 962WaterHCID 24638Chlorosulfonic acid2×HCID 59593442(3'S)-3-(3,5-dichlorophenyl)-1'-(3,5-difluorophenyl)-1,3'-bipyrrolidin-2'-one

Product 1

HCID 866377584-[(3'S)-3-(3,5-Dichlorophenyl)-2'-oxo-1,3'-bipyrrolidin-1'-yl]-2,6-difluorobenzene-1-sulfonyl chloride

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
50 °C

Procedure

Synthesized according to General Procedure 11. To a solution of (3′S)-3-(3,5-dichlorophenyl)-1′-(3,5-difluorophenyl)-1,3′-bipyrrolidin-2′-one (50 mg, 0.12 mmol) in DCE (0.4 mL) at 0° C. was added chlorosulfonic acid (71 mg, 40 μL, 0.61 mmol) dropwise and the reaction mixture stirred from 0° C. to RT over 1 hour, the temperature was raised to 50° C. and the reaction mixture stirred at this temperature for 2 hours. More chlorosulfonic acid was added (71 mg, 40 μL, 0.61 mmol) and the reaction mixture was stirred at 50° C. for 2 hours. The reaction mixture was poured into water and extracted with EtOAc (3×). The combined organic extracts were washed with saturated aqueous NaHCO3, water, and brine, dried (Na2SO4) and evaporated to dryness. The crude product was used without further purification in the next reaction step. (LC/MS (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)), m/z: M+1 obs=411.3; tR=1.46 min.

Workup

  1. customSynthesized
  2. stirringthe reaction mixture stirred at this temperature for 2 hours
  3. stirringthe reaction mixture was stirred at 50° C. for 2 hours
  4. extractionextracted with EtOAc (3×)
  5. washThe combined organic extracts were washed with saturated aqueous NaHCO3, water, and brine
  6. dry with materialdried (Na2SO4)
  7. customevaporated to dryness
  8. customThe crude product was used without further purification in the next reaction step

Sources & evidence

ORD record
ord-46cf70a3e2a843f1ab930520dbc00d26
Source dataset
uspto-grants-2012_03
Patent number
US08143297B2

Reaction notes

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