Phthalimide → 2-((5-(2-fluoro-5-methoxyphenyl)-6-isobutoxypyridin-2-yl)methyl)-1H-isoindole-1,3(2H)-dione

HRID 709615Notes

Reaction equation

HRID 709615 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[C:10]1[CH:11]=[CH:12][C:13]([CH2:21]O)=[N:14][C:15]=1[O:16][CH2:17][CH:18]([CH3:20])[CH3:19].[C:23]1(=[O:33])[NH:27][C:26](=[O:28])[C:25]2=[CH:29][CH:30]=[CH:31][CH:32]=[C:24]12.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C1COCC1.C1(C)C=CC=CC=1.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[C:10]1[CH:11]=[CH:12][C:13]([CH2:21][N:27]2[C:23](=[O:33])[C:24]3[C:25](=[CH:29][CH:30]=[CH:31][CH:32]=3)[C:26]2=[O:28])=[N:14][C:15]=1[O:16][CH2:17][CH:18]([CH3:19])[CH3:20]

Participants

8

Reactant 4

HCID 6809PhthalimideHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 117760235(5-(2-Fluoro-5-methoxyphenyl)-6-isobutoxypyridin-2-yl)methanol

Product 1

HCID 1177602692-((5-(2-fluoro-5-methoxyphenyl)-6-isobutoxypyridin-2-yl)methyl)-1H-isoindole-1,3(2H)-dioneYield 90.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (5-(2-fluoro-5-methoxyphenyl)-6-isobutoxypyridin-2-yl)methanol (177 mg) in THF (5.0 mL) was added phthalimide (102 mg), triphenylphosphine (181 mg) and a 40% solution of diethyl azodicarboxylate in toluene (320 μL), and the mixture was stirred at room temperature for 15 hr. Water was added, and the reaction mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (228 mg) as a colorless oil.

Workup

  1. extractionthe reaction mixture was extracted with ethyl acetate
  2. washThe extract was washed with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. customthe residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-b637d5188f3d4999b8554ece85100b58
Source dataset
uspto-grants-2015_11
Patent number
US09181186B2

Reaction notes

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