Water → HCID 58452431, compound

HRID 70689Notes

Reaction equation

HRID 70689 reaction equation
Cl[Si](C)(C)C.[I-].[K+].[CH:8]1([C:11]2[CH:12]=[CH:13][C:14]([CH:19]([C:27]3[CH:32]=[CH:31][C:30]([O:33][CH2:34][CH3:35])=[C:29]([F:36])[CH:28]=3)[CH2:20][C@@H:21]3[NH:25][C:24](=[O:26])[CH2:23][CH2:22]3)=[N:15][C:16]=2[O:17]C)[CH2:10][CH2:9]1.O>C(#N)C>[CH:8]1([C:11]2[C:16](=[O:17])[NH:15][C:14]([CH:19]([C:27]3[CH:32]=[CH:31][C:30]([O:33][CH2:34][CH3:35])=[C:29]([F:36])[CH:28]=3)[CH2:20][C@H:21]3[CH2:22][CH2:23][C:24](=[O:26])[NH:25]3)=[CH:13][CH:12]=2)[CH2:10][CH2:9]1

Participants

6

Reactant 4

HCID 962WaterHCID 4875Potassium IodideHCID 6397ChlorotrimethylsilaneHCID 67400762(5R)-5-[2-(5-cyclopropyl-6-methoxypyridin-2-yl)-2-(4-ethoxy-3-fluorophenyl)ethyl]pyrrolidin-2-one

Product 1

HCID 58452431HCID 58452431, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
50 °C

Procedure

Chlorotrimethylsilane (0.17 mL) and potassium iodide (370 mg) were added to a solution of (5R)-5-[2-(5-cyclopropyl-6-methoxypyridin-2-yl)-2-(4-ethoxy-3-fluorophenyl)ethyl]pyrrolidin-2-one (222 mg) in acetonitrile (4.4 mL) at room temperature, and then the mixture was stirred at 50° C. for one hour. Water was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with water and brine, dried over anhydrous magnesium sulfate and filtered, after which the solvent was evaporated under reduced pressure. One diastereomer (A) of the title compound was obtained as a white solid (71 mg, 33% (two steps)) by separating the residue by preparative HPLC (CHIRALPAK IB (20 mm i.d.×250 mm L, Daicel Chemical Industries, LTD.), 40° C., flow rate: 10 mL/min, ethanol:hexane=40:60) and concentrating the fraction eluted with a retention time of 13 minutes. The fraction eluted with a retention time of 28 minutes was concentrated to give the other diastereomer (B) of the title compound as a white solid (71 mg, 33% (two steps)).

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. washThe organic layer was washed with water and brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. customafter which the solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-4ce1bb5d0e3a4222a91f6cd07372f579
Source dataset
uspto-grants-2014_09
Patent number
US08822503B2

Reaction notes

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