N,N'-Dimethylethylenediamine → (R)-3-{4-[4-(3,5-dicyclopropylpyridin-2-yl)piperazine-1-carbonyl]phenyl}-4-ethyloxazolidin-2-one

HRID 1804244Notes

Reaction equation

HRID 1804244 reaction equation
[CH:1]1([C:4]2[C:5]([N:13]3[CH2:18][CH2:17][N:16]([C:19]([C:21]4[CH:26]=[CH:25][C:24](I)=[CH:23][CH:22]=4)=[O:20])[CH2:15][CH2:14]3)=[N:6][CH:7]=[C:8]([CH:10]3[CH2:12][CH2:11]3)[CH:9]=2)[CH2:3][CH2:2]1.[CH2:28]([C@@H:30]1[CH2:34][O:33][C:32](=[O:35])[NH:31]1)[CH3:29].C(=O)([O-])[O-].[K+].[K+].CNCCNC.[Cl-].[NH4+]>[Cu]I.C(OCC)(=O)C.C1(C)C=CC=CC=1>[CH:1]1([C:4]2[C:5]([N:13]3[CH2:18][CH2:17][N:16]([C:19]([C:21]4[CH:26]=[CH:25][C:24]([N:31]5[C@H:30]([CH2:28][CH3:29])[CH2:34][O:33][C:32]5=[O:35])=[CH:23][CH:22]=4)=[O:20])[CH2:15][CH2:14]3)=[N:6][CH:7]=[C:8]([CH:10]3[CH2:12][CH2:11]3)[CH:9]=2)[CH2:3][CH2:2]1

Participants

9

Reactant 5

HCID 8070N,N'-DimethylethylenediamineHCID 11430Potassium CarbonateHCID 25517Ammonium ChlorideHCID 641503(4R)-4-ethyl-1,3-oxazolidin-2-oneHCID 58484688[4-(3,5-Dicyclopropylpyridin-2-yl)piperazin-1-yl](4-iodophenyl)methanone

Product 1

HCID 46190230(R)-3-{4-[4-(3,5-dicyclopropylpyridin-2-yl)piperazine-1-carbonyl]phenyl}-4-ethyloxazolidin-2-oneYield 81.9%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of [4-(3,5-dicyclopropylpyridin-2-yl)piperazin-1-yl](4-iodophenyl)methanone (473 mg) described in Preparation Example 95, (R)-4-ethyloxazolidin-2-one (138 mg) described in Preparation Example 26, potassium carbonate (415 mg) and copper (I) iodide (38 mg) were added toluene (2 mL) and N,N′-dimethylethylenediamine (43 μL), and the mixture was heated under reflux for 3 hr. The reaction mixture was cooled, ethyl acetate and aqueous ammonium chloride solution were added and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with a 1:1 mixture of saturated aqueous ammonium chloride solution and ammonium water, washed once with saturated aqueous ammonium chloride solution, once with saturated aqueous sodium chloride solution, and dried over sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by column chromatography (chloroform:methanol) to give the title compound (377 mg).

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 3 hr
  3. temperatureThe reaction mixture was cooled
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe ethyl acetate layer was washed with a 1:1 mixture of saturated aqueous ammonium chloride solution and ammonium water
  6. washwashed once with saturated aqueous ammonium chloride solution, once with saturated aqueous sodium chloride solution
  7. dry with materialdried over sodium sulfate
  8. customThe solvent was evaporated under reduced pressure
  9. customThe residue was purified by column chromatography (chloroform:methanol)

Sources & evidence

ORD record
ord-264bbcee623b4fc2a64c0abe3ea7a320
Source dataset
uspto-grants-2013_01
Patent number
US08354401B2

Reaction notes

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