Cesium carbonate → (R)-3-{4-[4-(3,5-dimethylpyridin-2-yl)piperazine-1-carbonyl]-3-(2-oxopyrrolidin-1-yl)phenyl}-4-methyloxazolidin-2-one hydrochloride

HRID 1804282Notes

Reaction equation

HRID 1804282 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:14]([N:16]2[CH2:21][CH2:20][N:19]([C:22]3[C:27]([CH3:28])=[CH:26][C:25]([CH3:29])=[CH:24][N:23]=3)[CH2:18][CH2:17]2)=[O:15])=[C:6]([N:8]2[CH2:12][CH2:11][CH2:10][C:9]2=[O:13])[CH:7]=1.[CH3:30][C@@H:31]1[CH2:35][O:34][C:33](=[O:36])[NH:32]1.C(=O)([O-])[O-].[Cs+].[Cs+].C(P(C(C)(C)C)C1C(C)=C(C)C(C)=C(C)C=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C>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].O.C1(C)C=CC=CC=1>[ClH:1].[CH3:28][C:27]1[C:22]([N:19]2[CH2:20][CH2:21][N:16]([C:14]([C:5]3[CH:4]=[CH:3][C:2]([N:32]4[C@H:31]([CH3:30])[CH2:35][O:34][C:33]4=[O:36])=[CH:7][C:6]=3[N:8]3[CH2:12][CH2:11][CH2:10][C:9]3=[O:13])=[O:15])[CH2:17][CH2:18]2)=[N:23][CH:24]=[C:25]([CH3:29])[CH:26]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 2734858(R)-4-Methyloxazolidin-2-oneHCID 11953610Di-tert-butyl[3,4,5,6-tetramethyl-2',4',6'-tris(propan-2-yl)-[1,1'-biphenyl]-2-yl]phosphaneHCID 584846981-{5-Chloro-2-[4-(3,5-dimethylpyridin-2-yl)piperazine-1-carbonyl]phenyl}pyrrolidin-2-one

Product 1

HCID 67381171(R)-3-{4-[4-(3,5-dimethylpyridin-2-yl)piperazine-1-carbonyl]-3-(2-oxopyrrolidin-1-yl)phenyl}-4-methyloxazolidin-2-one hydrochlorideYield 34.8%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

To a mixture of 1-{5-chloro-2-[4-(3,5-dimethylpyridin-2-yl)piperazine-1-carbonyl]phenyl}pyrrolidin-2-one (206 mg) described in Preparation Example 121, (R)-4-methyloxazolidin-2-one (50.6 mg) described in Preparation Example 25, cesium carbonate (228 mg), tris(dibenzylideneacetone)dipalladium (0) chloroform (51.8 mg) and 2-di-tert-butylphosphino-3,4,5,6-tetramethyl-2′,4′,6′-triisopropyl-1,1′-biphenyl (24 mg) was added toluene (1 mL), and the mixture was refluxed for 8 hr. After cooling, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. After evaporation of the solvent, the residue was purified by column chromatography (ethyl acetate:methanol). The obtained compound was dissolved in ethyl acetate, 4N hydrogen chloride/ethyl acetate (0.13 mL) was added, and the precipitate was collected by filtration to give the title compound (89.3 mg).

Workup

  1. temperaturethe mixture was refluxed for 8 hr
  2. temperatureAfter cooling
  3. extractionthe mixture was extracted with ethyl acetate
  4. customAfter evaporation of the solvent
  5. customthe residue was purified by column chromatography (ethyl acetate:methanol)
  6. dissolutionThe obtained compound was dissolved in ethyl acetate
  7. addition4N hydrogen chloride/ethyl acetate (0.13 mL) was added
  8. filtrationthe precipitate was collected by filtration

Sources & evidence

ORD record
ord-253c6bea57744720812c6236380f2cf1
Source dataset
uspto-grants-2013_01
Patent number
US08354401B2

Reaction notes

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