Pyrrolidine → {4-Chloro-2-[5-chloro-2-(1-methyl-2-oxo-2-pyrrolidin-1-yl-ethoxy)-benzyl]-phenoxy}-acetic acid benzyl ester

HRID 2244475Notes

Reaction equation

HRID 2244475 reaction equation
[CH2:1]([O:8][C:9]([CH2:11][O:12][C:13]1[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][C:14]=1[CH2:15][C:16]1[CH:27]=[C:26]([Cl:28])[CH:25]=[CH:24][C:17]=1[O:18][CH:19]([CH3:23])[C:20]([OH:22])=O)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:34]1[CH:35]=CC2N(O)N=[N:40][C:38]=2[CH:39]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.N1CCCC1>C(#N)C>[CH2:1]([O:8][C:9](=[O:10])[CH2:11][O:12][C:13]1[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][C:14]=1[CH2:15][C:16]1[CH:27]=[C:26]([Cl:28])[CH:25]=[CH:24][C:17]=1[O:18][CH:19]([CH3:23])[C:20](=[O:22])[N:40]1[CH2:35][CH2:34][CH2:39][CH2:38]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 31268PyrrolidineHCID 682631,1'-CarbonyldiimidazoleHCID 757711-HydroxybenzotriazoleHCID 684525502-[2-(2-Benzyloxycarbonylmethoxy-5-chloro-benzyl)-4-chloro-phenoxy]-propionic acid2×

Product 1

HCID 68452258{4-Chloro-2-[5-chloro-2-(1-methyl-2-oxo-2-pyrrolidin-1-yl-ethoxy)-benzyl]-phenoxy}-acetic acid benzyl ester

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a suspension of 2-[2-(2-benzyloxycarbonylmethoxy-5-chloro-benzyl)-4-chloro-phenoxy]-propionic acid (Intermediate A) (100 mg, 0.204 mmol), HOBt (27.6 mg, 0.204 mmol) and PS-CDI (326.4 mg, 1.25 mmol/g, 0.408 mmol) in acetonitrile (15 mL) is added pyrrolidine (17.1 μL, 0.204 mmol). The reaction mixture is heated using microwave radiation in a Personal Chemistry Emrys™ Optimizer microwave reactor at 100° C. for 5 minutes. The PS-CDI resin is removed by filtration, rinsing with DCM and MeOH and the filtrate is concentrated in vacuo. The crude product is dissolved in EtOAc (50 mL) and washed with water (50 mL), aqueous sodium carbonate solution (30 mL), brine (50 mL) and then dried (MgSO4). The solvent is removed in vacuo and purification of the crude product by chromatography on silica eluting with EtOAc/iso-hexane (1:4) affords the titled product as a racemic mixture; MH+=542.

Workup

  1. temperatureThe reaction mixture is heated
  2. customat 100° C.
  3. customfor 5 minutes
  4. customThe PS-CDI resin is removed by filtration
  5. washrinsing with DCM and MeOH
  6. concentrationthe filtrate is concentrated in vacuo
  7. dissolutionThe crude product is dissolved in EtOAc (50 mL)
  8. washwashed with water (50 mL), aqueous sodium carbonate solution (30 mL), brine (50 mL)
  9. dry with materialdried (MgSO4)
  10. customThe solvent is removed in vacuo and purification of the crude product by chromatography on silica eluting with EtOAc/iso-hexane (1:4)

Sources & evidence

ORD record
ord-39ef2692d0f1431c9372a50e30aea9a6
Source dataset
uspto-grants-2010_03
Patent number
US07678826B2

Reaction notes

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