Cesium carbonate → (S)-2-(1-((5H-chromeno[3,4-c]pyridin-8-yl)oxy)-4-methylpentan-2-yl)isoindoline-1,3-dione

HRID 870899Notes

Reaction equation

HRID 870899 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[C:15]3[C:10](=[CH:11][N:12]=[CH:13][CH:14]=3)[CH2:9][O:8][C:6]=2[CH:7]=1.[OH:16][CH2:17][C@@H:18]([N:23]1[C:31](=[O:32])[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:24]1=[O:33])[CH2:19][CH:20]([CH3:22])[CH3:21].C(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:14]1[CH:13]=[N:12][CH:11]=[C:10]2[CH2:9][O:8][C:6]3[CH:7]=[C:2]([O:16][CH2:17][C@@H:18]([N:23]4[C:24](=[O:33])[C:25]5[C:30](=[CH:29][CH:28]=[CH:27][CH:26]=5)[C:31]4=[O:32])[CH2:19][CH:20]([CH3:22])[CH3:21])[CH:3]=[CH:4][C:5]=3[C:15]=12

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneHCID 713789222-[(2S)-1-Hydroxy-4-methylpentan-2-yl]-1H-isoindole-1,3(2H)-dioneHCID 866958928-chloro-5H-chromeno[3,4-c]pyridine

Product 1

HCID 86695893(S)-2-(1-((5H-chromeno[3,4-c]pyridin-8-yl)oxy)-4-methylpentan-2-yl)isoindoline-1,3-dioneYield 101.7%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred suspension of 8-chloro-5H-chromeno[3,4-c]pyridine (1 g, 4.59 mmol), (S)-2-(1-hydroxy-4-methylpentan-2-yl)isoindoline-1,3-dione (3.43 g, 13.88 mmol), di-tert-butyl(2′,4′,6′-triisopropyl-[1,1′-biphenyl]-2-yl)phosphine (1.17 g, 2.76 mmol) and cesium carbonate (2.245 g, 6.89 mmol) in toluene (4 mL) was added palladium (II) acetate (0.309 g, 1.38 mmol). Nitrogen gas was bubbled through the mixture for 5 min, and then the mixture was heated at 80° C. for 14 h. The reaction was diluted with ethyl acetate (25 mL) and filtered through celite. The filtrate was washed with water (1×20 mL) and brine (1×20 mL), dried over sodium sulfate and concentrated under reduced pressure. The residue was purified via silica gel column chromatography (60% ethyl acetate in hexanes) to afford (5)-2-(1-((5H-chromeno[3,4-c]pyridin-8-yl)oxy)-4-methylpentan-2-yl)isoindoline-1,3-dione (2 g, 4.67 mmol, quantitative yield) as a semi solid. LCMS (ESI) m/e 429 [(M+H)+, calcd for C26H25N2O4 429.2].

Workup

  1. customNitrogen gas was bubbled through the mixture for 5 min
  2. additionThe reaction was diluted with ethyl acetate (25 mL)
  3. filtrationfiltered through celite
  4. washThe filtrate was washed with water (1×20 mL) and brine (1×20 mL)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified via silica gel column chromatography (60% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-2d10fb7a7aeb4aa5afc0c321155b4b85
Source dataset
uspto-grants-2015_03
Patent number
US08969564B2

Reaction notes

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