Diiodomethane → (R)-4-((R)-2-cyclopropyl-1-hydroxyethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one

HRID 2208975Notes

Reaction equation

HRID 2208975 reaction equation
[OH:1][C@@H:2]([C@H:6]1[CH2:10][N:9]([C@@H:11]([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)[CH3:12])[C:8](=[O:21])[CH2:7]1)[CH2:3][CH:4]=[CH2:5].[CH2:22]([Zn]CC)C.ICI>>[CH:4]1([CH2:3][C@H:2]([C@H:6]2[CH2:10][N:9]([C@@H:11]([C:13]3[CH:14]=[CH:15][C:16]([O:19][CH3:20])=[CH:17][CH:18]=3)[CH3:12])[C:8](=[O:21])[CH2:7]2)[OH:1])[CH2:22][CH2:5]1

Participants

4

Reactant 3

HCID 6346DiiodomethaneHCID 117843150(R)-4-((R)-1-hydroxybut-3-enyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-oneHCID 178418750HCID 178418750, compound

Product 1

HCID 117843169(R)-4-((R)-2-cyclopropyl-1-hydroxyethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one

Procedure

To a solution of (R)-4-((R)-1-hydroxybut-3-enyl)-1-4R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one 1.08 (145 mg, 0.50 mmol) at 0° C. was added 1M diethyl zinc (2.51 ml, 2.51 mmol). Diiodomethane (0.404 ml, 5.01 mmol) was added, and the mixture was stirred at rt for 60 min and quenched by the addition of sat NH4Cl (10 mL). EtOAc was added, stirred 5 min and the layers were separated. The aqueous layer was extracted with EtOAc (2×10 mL) and the combined organics were dried (MgSO4), filtered and concentrated. The residue was purified by flash chromatography (20-->100% EtOAc in hexanes) to afford (R)-4-((R)-2-cyclopropyl-1-hydroxyethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one 1.09.

Workup

  1. customquenched by the addition of sat NH4Cl (10 mL)
  2. additionEtOAc was added
  3. stirringstirred 5 min
  4. customthe layers were separated
  5. extractionThe aqueous layer was extracted with EtOAc (2×10 mL)
  6. dry with materialthe combined organics were dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by flash chromatography (20-->100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-6b1e2f6a223c49af95629057239c6d93
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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