Potassium Carbonate → methyl 5-[(E)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethenyl]-2-(propan-2-yloxy)pyridine-4-carboxylate

HRID 577540Notes

Reaction equation

HRID 577540 reaction equation
Br[C:2]1[C:3]([C:12]([O:14][CH3:15])=[O:13])=[CH:4][C:5]([O:8][CH:9]([CH3:11])[CH3:10])=[N:6][CH:7]=1.[CH:16]([N:18]1[C:22](=[O:23])[C:21]2=[CH:24][CH:25]=[CH:26][CH:27]=[C:20]2[C:19]1=[O:28])=[CH2:17].C([O-])([O-])=O.[K+].[K+]>C1(C)C=CC=CC=1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[O:28]=[C:19]1[C:20]2[C:21](=[CH:24][CH:25]=[CH:26][CH:27]=2)[C:22](=[O:23])[N:18]1/[CH:16]=[CH:17]/[C:2]1[C:3]([C:12]([O:14][CH3:15])=[O:13])=[CH:4][C:5]([O:8][CH:9]([CH3:11])[CH3:10])=[N:6][CH:7]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 770351H-Isoindole-1,3(2H)-dione, 2-ethenyl-HCID 86723769HCID 86723769, compound

Product 1

HCID 86723770methyl 5-[(E)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethenyl]-2-(propan-2-yloxy)pyridine-4-carboxylateYield 34.3%

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of methyl 5-bromo-2-(propan-2-yloxy)pyridine-4-carboxylate (112a, 3.40 g, 12.4 mmol) and N-vinylphthalimide (2.58 g, 14.9 mmol) in toluene (124 mL) was added K2CO3 (5.19 g, 37.2 mmol) followed by Pd(P(tBu)3)2 (0.400 g, 0.775 mmol). The reaction mixture was degassed and heated in a sealed tube at 110° C. for 18 hours. The reaction mixture was cooled to room temperature and filtered through CELITE®. H2O (100 mL) was added, the organic layer was separated and concentrated under vacuum, and the residue was purified by column chromatography (0-80%, ethyl acetate/heptanes) to give methyl 5-[(E)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethenyl]-2-(propan-2-yloxy)pyridine-4-carboxylate (112b, 1.56 g, 34%) as yellow solid.

Workup

  1. customThe reaction mixture was degassed
  2. temperatureThe reaction mixture was cooled to room temperature
  3. filtrationfiltered through CELITE®
  4. additionH2O (100 mL) was added
  5. customthe organic layer was separated
  6. concentrationconcentrated under vacuum
  7. customthe residue was purified by column chromatography (0-80%, ethyl acetate/heptanes)

Sources & evidence

ORD record
ord-6a1c3afdff394f9980b3d6a1b061bff8
Source dataset
uspto-grants-2015_05
Patent number
US09040515B2

Reaction notes

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