N-Hydroxyphthalimide → 2-[2-(2,2-Dimethyl-[1,3]dioxolan-4-yl)-ethoxy]-isoindole-1,3-dione

HRID 2218440Notes

Reaction equation

HRID 2218440 reaction equation
[CH3:1][C:2]1([CH3:10])[O:6][CH:5]([CH:7](O)[CH3:8])[CH2:4][O:3]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[OH:30][N:31]1[C:35](=[O:36])[C:34]2=[CH:37][CH:38]=[CH:39][CH:40]=[C:33]2[C:32]1=[O:41].CCOC(/N=N/C(OCC)=O)=O>O1CCCC1>[CH3:10][C:2]1([CH3:1])[O:6][CH:5]([CH2:7][CH2:8][O:30][N:31]2[C:35](=[O:36])[C:34]3[C:33](=[CH:40][CH:39]=[CH:38][CH:37]=3)[C:32]2=[O:41])[CH2:4][O:3]1

Participants

6

Reactant 4

HCID 10665N-HydroxyphthalimideHCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 122412841-(2,2-Dimethyl-1,3-dioxolan-4-yl)ethanol

Product 1

HCID 222862962-[2-(2,2-Dimethyl-[1,3]dioxolan-4-yl)-ethoxy]-isoindole-1,3-dioneYield 58.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a vigorously stirring suspension of 1,2,4-butanetriol (5.8 g, 54.6 mmol) in dichloromethane (20 mL) was added 2,2-dimethoxypropane (6.8 mL, 54.6 mmol) and catalytic p-toluenesulfonic acid. After 5 minutes, the solution became homogenous and was allowed to stir for an additional 30 minutes. The reaction mixture was then concentrated in vacuo to afford (2,2-Dimethyl-[1,3]dioxolan-4-yl)-ethanol (7.72 g, 96.7%). To a stirring solution of (2,2-Dimethyl-[1,3]dioxolan-4-yl)-ethanol (6.95 g, 47.5 mmol), triphenylphosphine (12.5 g, 47.5 mmol) and N-hydroxyphthalimide in freshly distilled tetrahydrofuran (200 mL) at 0° C. was slowly added (over 20 minutes) diethylazodicarboxylate. The dark red solution was allowed to stir for 2 hours at 0° C. and then allowed to warm to room temperature while stirring for 17 hours. The yellow solution was concentrated in vacuo and dissolved in chloroform (100 mL). The solids were filtered and filtrate concentrated. This filtration was repeated twice. The remaining yellow oil was purified on silica gel eluting with hexanes-ethyl acetate (4:1) to afford 2-[2-(2,2-Dimethyl-[1,3]dioxolan-4-yl)-ethoxy]-isoindole-1,3-dione (8.1 g, 58.7%). To a stirring solution of 2-[2-(2,2-Dimethyl-[1,3]dioxolan-4-yl)-ethoxy]-isoindole-1,3-dione (0.86 g, 2.95 mmol) in dichloromethane (10 mL) at 0° C. was added methylhydrazine (0.16 mL, 2.95 mmol). The resultant solution was allowed to warm to room temperature and stirred for 3 days. The resulting suspension was diluted with diethyl ether (20 mL) and filtered. The filtrate concentrated in vacuo to afford O-(2,2-dimethyl-[1,3]dioxolan-4-ylethyl)-hydroxylamine (0.36 g, 75.3%): 1H-NMR (400 MHz; CDCl3) δ 4.18 (quint, 1H, J=5.9), 4.07 (dd, 1H, J=5.9, 7.8), 3.86 (t, 2H, J=6.2), 3.56 (t, 1H, J=7.6), 1.89 (m, 2H), 1.36 (s, 3H), 1.20 (s, 3H); MS(APCI+)=162.

Workup

  1. temperatureto warm to room temperature
  2. stirringwhile stirring for 17 hours
  3. concentrationThe yellow solution was concentrated in vacuo
  4. dissolutiondissolved in chloroform (100 mL)
  5. filtrationThe solids were filtered
  6. concentrationfiltrate concentrated
  7. filtrationThis filtration
  8. customThe remaining yellow oil was purified on silica gel eluting with hexanes-ethyl acetate (4:1)

Sources & evidence

ORD record
ord-7147f28496d34a00aaf9341b5cdc9d43
Source dataset
uspto-grants-2008_08
Patent number
US07411001B2

Reaction notes

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