Phthalimide → 2-((1-(Benzhydryloxy)-5-((4-methoxybenzyl)oxy)-4-oxo-1,4-dihydropyridin-2-yl)methyl)isoindoline-1,3-dione

HRID 627292Notes

Reaction equation

HRID 627292 reaction equation
[CH:1]([O:14][N:15]1[CH:20]=[C:19]([O:21][CH2:22][C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=2)[C:18](=[O:31])[CH:17]=[C:16]1[CH2:32]O)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:34]1(=[O:44])[NH:38][C:37](=[O:39])[C:36]2=[CH:40][CH:41]=[CH:42][CH:43]=[C:35]12.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1COCC1.CN(C=O)C>[CH:1]([O:14][N:15]1[CH:20]=[C:19]([O:21][CH2:22][C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=2)[C:18](=[O:31])[CH:17]=[C:16]1[CH2:32][N:38]1[C:34](=[O:44])[C:35]2[C:36](=[CH:40][CH:41]=[CH:42][CH:43]=2)[C:37]1=[O:39])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 6809PhthalimideHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 156277671-Diphenylmethyloxy-5 p-methoxybenzyloxy-2-hydroxymethyl-4-pyridone2×

Product 1

HCID 150932422-((1-(Benzhydryloxy)-5-((4-methoxybenzyl)oxy)-4-oxo-1,4-dihydropyridin-2-yl)methyl)isoindoline-1,3-dioneYield 64.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-(benzhydryloxy)-2-(hydroxymethyl)-5-((4-methoxybenzyl)oxy)pyridin-4(1H)-one (Intermediate 291, 2 g, 4.51 mmol), phthalimide (0.664 g, 4.51 mmol) and triphenylphosphine (1.178 g, 4.51 mmol) in THF (20 mL) at room temperature was added diisopropyl azodicarboxylate (2.397 mL, 12.18 mmol). Reagents are insoluble. DMF (10 mL) was added. The reaction was stirred at room temperature overnight. The reaction mixture was filtered and concentrated onto silica gel. Silica gel chromatography (0%-4% methanol/dichloromethane) did not offer separation of desired product from impurities. Fractions were combined and repurified. Silica gel chromatography (0%-30% acetone/dichloromethane) afforded the title compound (1.66 g, 64.3%) as a light yellow foam.

Workup

  1. filtrationThe reaction mixture was filtered
  2. concentrationconcentrated onto silica gel
  3. customseparation of desired product from impurities
  4. customrepurified

Sources & evidence

ORD record
ord-1688937bfc614b469c02839d759a1e2e
Source dataset
uspto-grants-2016_04
Patent number
US09309245B2

Reaction notes

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