N-Hydroxyphthalimide → 2,2-Dimethyl-1,3-dioxan-5-ol

HRID 2181486Notes

Reaction equation

HRID 2181486 reaction equation
[CH3:1][C:2]1([CH3:9])[O:7][CH2:6][CH:5]([OH:8])[CH2:4][O:3]1.[OH:10][N:11]1[C:15](=[O:16])[C:14]2=[CH:17][CH:18]=[CH:19][CH:20]=[C:13]2[C:12]1=[O:21].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[CH3:1][C:2]1([CH3:9])[O:7][CH2:6][CH:5]([OH:8])[CH2:4][O:3]1.[CH3:1][C:2]1([CH3:9])[O:7][CH2:6][CH:5]([O:10][N:11]2[C:12](=[O:21])[C:13]3[C:14](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15]2=[O:16])[CH2:4][O:3]1

Participants

7

Reactant 4

HCID 10665N-HydroxyphthalimideHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 110298842,2-Dimethyl-1,3-dioxan-5-ol

Product 2

HCID 110298842,2-Dimethyl-1,3-dioxan-5-olHCID 220256752-(2,2-Dimethyl-[1,3]dioxan-5-yloxy)-isoindole-1,3-dione

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2,2-Dimethyl-[1,3]dioxan-5-ol was prepared as described previously (Forbes, D. C. et al.; Synthesis, 1998;6:879-882). 1H NMR (400 MHz; DMSO-d6) δ 4.91 (d, 1 H, J=5.1), 3.70-3.75 (m, 2 H), 3.41-3.46 (m, 3 H), 1.30 (s, 3 H), 1.24 (s, 3 H); MS (APCI+)=132.9. To a stirring solution of 2,2-dimethyl-[1,3]dioxan-5-ol (1.50 g, 11.35 mmol), N-hydroxyphthalimide (1.85 g, 11.35 mmol), and triphenylphosphine (2.98 g, 11.35 mmol) in anhydrous tetrahydrofuran (30 mL) at 0° C. was added diethyl azodicarboxylate (2.3 mL, 14.75 mmol). The resultant solution was allowed to warm to room temperature. After stirring for 3 hours, the mixture was concentrated in vacuo and charged with chloroform affording white solids. The solids were filtered off and filtrate was collected and concentrated. The residue was purified via silica column chromatography (4:1 hexanes/ethyl acetate) affording 2-(2,2-dimethyl-[1,3]dioxan-5-yloxy)-isoindole-1,3-dione as clear crystals (1.74 g, 55% over 2 steps): 1H NMR (400 MHz; DMSO-d6) δ 7.83 (s, 4H), 4.11-4.12 (m, 1H), 4.04-4.09 (m, 2H), 3.92-3.96 (m, 2H), 1.32 (s, 3H), 1.25 (s, 3H); MS (APCI+)=278.0.

Workup

  1. custom(Forbes, D. C. et al.; Synthesis, 1998;6:879-882)
  2. concentrationthe mixture was concentrated in vacuo
  3. additioncharged with chloroform affording white solids
  4. filtrationThe solids were filtered off
  5. customfiltrate was collected
  6. concentrationconcentrated
  7. customThe residue was purified via silica column chromatography (4:1 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-f754b81ca3f444628a9edb9f1dad1264
Source dataset
uspto-grants-2005_05
Patent number
US06891066B2

Reaction notes

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