N-Hydroxyphthalimide → 2-[2-(2,2,2-Trifluoro-ethylamino)-ethoxy]-isoindole-1,3-dione

HRID 1062306Notes

Reaction equation

HRID 1062306 reaction equation
CCOC(/N=N/C(OCC)=O)=O.[F:13][C:14]([F:22])([F:21])[CH2:15][NH:16][CH2:17][CH2:18][O:19][NH2:20].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.ON1[C:47](=[O:48])[C:46]2=[CH:49][CH:50]=[CH:51][CH:52]=[C:45]2[C:44]1=[O:53]>>[F:13][C:14]([F:22])([F:21])[CH2:15][NH:16][CH2:17][CH2:18][O:19][N:20]1[C:47](=[O:48])[C:46]2[C:45](=[CH:52][CH:51]=[CH:50][CH:49]=2)[C:44]1=[O:53]

Participants

5

Reactant 4

HCID 10665N-HydroxyphthalimideHCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 22286011O-[2-(2,2,2-trifluoro-ethylamino)-ethyl]-hydroxylamine

Product 1

HCID 222861382-[2-(2,2,2-Trifluoro-ethylamino)-ethoxy]-isoindole-1,3-dioneYield 63%

Procedure

Diethylazodicarboxylate (3.60 mL, 22.9 mmol) was added dropwise over 30 min to a solution comprised of O-[2-(2,2,2-trifluoro-ethylamino)-ethyl]-hydroxylamine (3.19 g, 22.3 mmol, prepared as in J. Am. Chem. Soc. 1979, 101, 4300), triphenylphosphine (6.05 g, 23.1 mmol), and N-hydroxyphthalimide (3.65 g, 22.4 mmol). The resultant reaction mixture was stirred at ambient temperature. After 20 h, the reaction mixture was concentrated and the residue was dissolved in 60 mL of warm chloroform. Upon cooling, crystallization of diethyl 1,2-hydrazaine dicarboxylate ensued. The precipitate was filtered and the filtrate was concentrated and further diluted with ether. A single crystal of triphenylphosphine oxide was added, initiating copious precipitation. The resultant precipitate was removed by filtration and the filtrate was concentrated in vacuo and chromatographed on silica gel. Elution with hexanes-ethyl acetate (2:1) afforded 2-[2-(2,2,2-trifluoro-ethylamino)-ethoxy]-isoindole-1,3-dione (4.05 g, 63% yield) as a colorless oil: 1H NMR (400 Mz, CDCl3) δ 7.84-7.73 (m, 4H), 4.30 (t, J=4.8 Hz, 2H), 3.26 (q, J=9.5 Hz, 2H), 3.00 (t, J=4.9 Hz, 2H), 2.33 (br s, 1H); MS (APCI+)=289.0.

Workup

  1. customThe resultant reaction mixture
  2. concentrationthe reaction mixture was concentrated
  3. dissolutionthe residue was dissolved in 60 mL of warm chloroform
  4. temperatureUpon cooling
  5. customcrystallization of diethyl 1,2-hydrazaine dicarboxylate
  6. filtrationThe precipitate was filtered
  7. concentrationthe filtrate was concentrated
  8. additionfurther diluted with ether
  9. additionA single crystal of triphenylphosphine oxide was added
  10. customprecipitation
  11. customThe resultant precipitate was removed by filtration
  12. concentrationthe filtrate was concentrated in vacuo
  13. customchromatographed on silica gel
  14. washElution with hexanes-ethyl acetate (2:1)

Sources & evidence

ORD record
ord-b074c9768145451d908d1ed579dbfbc1
Source dataset
uspto-grants-2005_11
Patent number
US06960614B2

Reaction notes

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