N-Hydroxyphthalimide → 2-(tetrahydro-2H-pyran-4-yloxy)-1H-isoindole-1,3(2H)-dione

HRID 29162

Reaction equation

HRID 29162 reaction equation
[OH:1][N:2]1[C:6](=[O:7])[C:5]2=[CH:8][CH:9]=[CH:10][CH:11]=[C:4]2[C:3]1=[O:12].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[O:32]1[CH2:37][CH2:36][CH:35](O)[CH2:34][CH2:33]1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O>C1COCC1>[O:32]1[CH2:37][CH2:36][CH:35]([O:1][N:2]2[C:3](=[O:12])[C:4]3[C:5](=[CH:8][CH:9]=[CH:10][CH:11]=3)[C:6]2=[O:7])[CH2:34][CH2:33]1

Participants

6

Reactant 4

HCID 10665N-HydroxyphthalimideHCID 11776TriphenylphosphineHCID 74956Tetrahydro-4H-pyran-4-olHCID 97268Di-tert-butyl azodicarboxylate

Product 1

HCID 229971882-(tetrahydro-2H-pyran-4-yloxy)-1H-isoindole-1,3(2H)-dione

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A light suspension containing N-hydroxylphthalimide (18.4 mmol, 3.0 g), triphenylphosphine (18.4 mmol, 4.82 g), tetrahydro-4H-pyran-4-ol (18.4 mmol, 1.75 mL) and anhydrous THF (50 mL), were transferred to a flask containing di-tert-butyl azodicarboxylate (20.2 mmol, 4.66 g) under nitrogen. Over 2 hours the reaction stirred at room temperature and changed from a dark orange to yellow in appearance. The solvent was removed under vacuum and replaced with trifluoroacetic acetic acid (10 mL). The reaction was stirred for 30 minutes and the TFA was removed under vacuum. The crude residue was then dissolved in ethyl acetate, washed with a saturated aqueous solution of sodium bicarbonate, 5% aqueous solution of potassium carbonate, brine and dried over magnesium sulfate. The solvent was removed under vacuum and the residual triphenylphosphine oxide was crystallized and filtered using hexanes and ether. The solvent was again removed and the crude solid was purified by silica gel chromatography (2:1 hexanes/ethyl acetate) and recrystallization using methylene chloride and hexanes providing 1.69 g (37%) of a white crystal. Rf=0.3 (2:1 hexanes/ethyl acetate); H1-NMR (CDCl3): δ 7.84-7.82 (2H,m), 7.75-7.73(2H,m), 4.46-4.40 (1H,m), 4.08-4.02 (2H,m), 3.50-3.44 (2H,m), 2.04-1.98 (2H,m), 1.92-1.84 (2H,m).

Workup

  1. customwere transferred to a flask
  2. customThe solvent was removed under vacuum
  3. stirringThe reaction was stirred for 30 minutes
  4. customthe TFA was removed under vacuum
  5. dissolutionThe crude residue was then dissolved in ethyl acetate
  6. washwashed with a saturated aqueous solution of sodium bicarbonate, 5% aqueous solution of potassium carbonate, brine
  7. dry with materialdried over magnesium sulfate
  8. customThe solvent was removed under vacuum
  9. customthe residual triphenylphosphine oxide was crystallized
  10. filtrationfiltered
  11. customThe solvent was again removed
  12. customthe crude solid was purified by silica gel chromatography (2:1 hexanes/ethyl acetate) and recrystallization

Sources & evidence

ORD record
ord-fce6c1405a3f40fe8d7a6b21743c7f28
Source dataset
uspto-grants-2008_09
Patent number
US07419967B2

Linked notes

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