Cesium carbonate → 2-Butyl-5-(4-phenylpyridin-3-yloxy)isoindolin-1-one

HRID 1878634Notes

Reaction equation

HRID 1878634 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[CH2:14]([N:18]1[CH2:26][C:25]2[C:20](=[CH:21][CH:22]=[C:23]([OH:27])[CH:24]=2)[C:19]1=[O:28])[CH2:15][CH2:16][CH3:17].C([O-])([O-])=O.[Cs+].[Cs+].CC(C)(C(=O)CC(=O)C(C)(C)C)C>CN1CCCC1=O.[Cu]I.C(OCC)(=O)C.O>[CH2:14]([N:18]1[CH2:26][C:25]2[C:20](=[CH:21][CH:22]=[C:23]([O:27][C:2]3[CH:3]=[N:4][CH:5]=[CH:6][C:7]=3[C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=3)[CH:24]=2)[C:19]1=[O:28])[CH2:15][CH2:16][CH3:17]

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 707002,2,6,6-Tetramethyl-3,5-heptanedioneHCID 27629283-Bromo-4-phenylpyridineHCID 138973842-Butyl-5-hydroxyisoindolin-1-one

Product 1

HCID 534772442-Butyl-5-(4-phenylpyridin-3-yloxy)isoindolin-1-oneYield 21%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
220 °C

Procedure

A mixture of 3-bromo-4-phenylpyridine (50 mg, 0.213 mmol), 2-butyl-5-hydroxy-isoindolin-1-one (88 mg, 0.427 mmol), Cs2CO3 (139 mg, 0.427 mmol), CuI (16.3 mg, 0.085 mmol) and 2,2,6,6-tetramethyl-3.5-heptanedione (53 μL, 0.256 mmol) in degassed N-methylpyrrolidone (NMP) (2 mL) was stirred and heated in the microwave (220° C., 300 W, 30 min). Two of those reactions were combined, excess water and ethyl acetate were added. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were extracted with aqueous HCl (2 M) and the combined extracts were basified with aqueous NaOH (2 M) followed by extraction with ethyl acetate. The combined organic layers were washed with water and dried over MgSO4. Purification by HPLC provided 2-butyl-5-(4-phenylpyridin-3-yloxy)isoindolin-1-one (16 mg, 8%).

Workup

  1. customThe organic layer was separated
  2. extractionthe aqueous layer was extracted with ethyl acetate
  3. extractionThe combined organic layers were extracted with aqueous HCl (2 M)
  4. extractionfollowed by extraction with ethyl acetate
  5. washThe combined organic layers were washed with water
  6. dry with materialdried over MgSO4
  7. customPurification by HPLC

Sources & evidence

ORD record
ord-1db14dfe5fcf4e5595c7e889eae89bac
Source dataset
uspto-grants-2012_11
Patent number
US08314120B2

Reaction notes

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