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

HRID 2261486Notes

Reaction equation

HRID 2261486 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N:9]2[CH2:13][CH2:12][C@@H:11](O)[C:10]2=[O:15])[CH:5]=[C:6]([F:8])[CH:7]=1.CCN(C(C)C)C(C)C.[Cl:25][C:26]1[CH:27]=[C:28]([CH:33]2[CH2:37][CH2:36][NH:35][CH2:34]2)[CH:29]=[C:30]([Cl:32])[CH:31]=1.O>C(Cl)Cl>[Cl:25][C:26]1[CH:27]=[C:28]([CH:33]2[CH2:37][CH2:36][N:35]([C@H:11]3[CH2:12][CH2:13][N:9]([C:4]4[CH:3]=[C:2]([F:1])[CH:7]=[C:6]([F:8])[CH:5]=4)[C:10]3=[O:15])[CH2:34]2)[CH:29]=[C:30]([Cl:32])[CH:31]=1

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 595934543-(3,5-Dichlorophenyl)pyrrolidineHCID 59593460(R)-1-(3,5-difluorophenyl)-3-hydroxypyrrolidin-2-one

Product 1

HCID 59593442(3'S)-3-(3,5-dichlorophenyl)-1'-(3,5-difluorophenyl)-1,3'-bipyrrolidin-2'-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-20 °C

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%).

Workup

  1. customSynthesized
  2. additionfollowed by the dropwise addition of triflic anyhydride (282 mg, 168 μL, 1.0 mmol)
  3. stirringthe reaction mixture was stirred at −20° C. for 16 hours
  4. extractionextracted with EtOAc (3 ×)
  5. washThe combined organic phases were washed with brine
  6. dry with materialdried (Na2SO4)
  7. customevaporated to dryness
  8. customPurification by silica gel chromatography (0-20% EtOAC in DCM)

Sources & evidence

ORD record
ord-7441e0008aff46b8b98aa8dddb20024b
Source dataset
uspto-grants-2010_12
Patent number
US07846954B2

Reaction notes

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