Cesium carbonate → 2-chloro-4-[(2S,3S)-3-hydroxy-2,3-dimethyl-5-oxopyrrolidin-1-yl]-3-methylbenzonitrile

HRID 1967390Notes

Reaction equation

HRID 1967390 reaction equation
[Cl:1][C:2]1[C:9]([CH3:10])=[C:8](I)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[OH:12][C@:13]1([CH3:20])[C@H:17]([CH3:18])[NH:16][C:15](=[O:19])[CH2:14]1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:1][C:2]1[C:9]([CH3:10])=[C:8]([N:16]2[C:15](=[O:19])[CH2:14][C@@:13]([OH:12])([CH3:20])[C@@H:17]2[CH3:18])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 167319952-Chloro-4-iodo-3-methylbenzonitrileHCID 55299894(4S,5S)-4-hydroxy-4,5-dimethylpyrrolidin-2-one

Product 1

HCID 595569112-chloro-4-[(2S,3S)-3-hydroxy-2,3-dimethyl-5-oxopyrrolidin-1-yl]-3-methylbenzonitrileYield 56%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A solution of 2-chloro-4-iodo-3-methylbenzonitrile (1.29 g), (4S,5S)-4-hydroxy-4,5-dimethylpyrrolidin-2-one (500 mg), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (343 mg), tris(dibenzylideneacetone)dipalladium(0) (177 mg) and cesium carbonate (1.86 g) in 1,4-dioxane (4 mL) was tightly sealed, and the mixture was stirred at 120° C. for 3 hr using microwave reactor. The reaction mixture was filtered through silica gel, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: ethyl acetate/hexane=30→70%, basic silica gel eluent: ethyl acetate/hexane=30→80%), and the obtained solid was recrystallized from ethyl acetate/hexane to give the title compound as colorless crystals (yield: 603 mg, 56%).

Workup

  1. filtrationThe reaction mixture was filtered through silica gel
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. customThe residue was purified by silica gel column chromatography (eluent: ethyl acetate/hexane=30→70%, basic silica gel eluent: ethyl acetate/hexane=30→80%)
  4. customthe obtained solid was recrystallized from ethyl acetate/hexane

Sources & evidence

ORD record
ord-fe3ffa5f46a4400bb162335683314f38
Source dataset
uspto-grants-2013_04
Patent number
US08420694B2

Reaction notes

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