N-Hydroxyphthalimide → (R)-2-((1,4-dioxan-2-yl)methoxy)isoindoline-1,3-dione

HRID 1917466Notes

Reaction equation

HRID 1917466 reaction equation
[O:1]1[CH2:6][CH2:5][O:4][CH2:3][C@@H:2]1[CH2:7][OH:8].O[N:10]1[C:14](=[O:15])[C:13]2=[CH:16][CH:17]=[CH:18][CH:19]=[C:12]2[C:11]1=[O:20].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>[O:1]1[CH2:6][CH2:5][O:4][CH2:3][C@@H:2]1[CH2:7][O:8][N:10]1[C:14](=[O:15])[C:13]2[C:12](=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:11]1=[O:20]

Participants

6

Reactant 4

HCID 10665N-HydroxyphthalimideHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 44429359(S)-(1,4-Dioxan-2-yl)methanol

Product 1

HCID 57999306(R)-2-((1,4-dioxan-2-yl)methoxy)isoindoline-1,3-dione

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

2K (1.33 g, 11.2 mmol), N-hydroxyphthalimide (2.02 g, 12.4 mmol), triphenylphosphine (3.25 g, 12.4 mmol) were dissolved in 30 mL of dry THF and the mixture was cooled in an ice bath. Diisopropyl azodicarboxylate (2.51 g, 12.4 mmol) in 5 mL of THF was added to the above mixture dropwise. After the addition was complete, the ice bath was removed and the reaction was stirred at room temp overnight. Next day, the reaction was done. It was concentrated in vacuo to an oil and then purified on flash column chromatography using ethyl acetate/hexane 20/80 to give (R)-2-((1,4-dioxan-2-yl)methoxy)isoindoline-1,3-dione (2L). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 3.56 (t, J=10.74 Hz, 1H) 3.60-3.85 (m, 4H) 3.92 (dd, J=11.75, 2.40 Hz, 1H) 4.05 (ddd, J=9.98, 3.03, 2.91 Hz, 1H) 4.11-4.19 (m, 1H) 4.20-4.29 (m, 1H) 7.71-7.80 (m, 2H) 7.81-7.91 (m, 2H).

Workup

  1. temperaturethe mixture was cooled in an ice bath
  2. additionAfter the addition
  3. customthe ice bath was removed
  4. concentrationIt was concentrated in vacuo to an oil
  5. custompurified on flash column chromatography

Sources & evidence

ORD record
ord-2cc8f58686e24553bc3d0ad7413f5033
Source dataset
uspto-grants-2013_12
Patent number
US08618290B2

Reaction notes

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