N-Hydroxyphthalimide → Tert-butyl 2-(1,3-dioxoisoindolin-2-yloxy)ethyl(methyl)carbamate

HRID 2218459Notes

Reaction equation

HRID 2218459 reaction equation
CCOC(/N=N/C(OCC)=O)=O.[C:13]([O:17][C:18](=[O:24])[N:19]([CH2:21][CH2:22][OH:23])[CH3:20])([CH3:16])([CH3:15])[CH3:14].O[N:26]1[C:30](=[O:31])[C:29]2=[CH:32][CH:33]=[CH:34][CH:35]=[C:28]2[C:27]1=[O:36].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCCC1>[C:13]([O:17][C:18](=[O:24])[N:19]([CH2:21][CH2:22][O:23][N:26]1[C:30](=[O:31])[C:29]2[C:28](=[CH:35][CH:34]=[CH:33][CH:32]=2)[C:27]1=[O:36])[CH3:20])([CH3:16])([CH3:14])[CH3:15]

Participants

6

Reactant 4

HCID 10665N-HydroxyphthalimideHCID 11776TriphenylphosphineHCID 545700N-(tert-Butoxycarbonyl)-N-methyl-2-aminoethanolHCID 5462977Diethyl azodicarboxylate

Product 1

HCID 59846673Tert-butyl 2-(1,3-dioxoisoindolin-2-yloxy)ethyl(methyl)carbamateYield 98.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Diethylazodicarboxylate was added dropwise over 45 min to a stirring solution of (2-hydroxy-ethyl)-methyl-carbamic acid tert-butyl ester (7.10 g, 40.5 mmol), N-hydroxyphthalimide (7.17 g, 44.0 mmol) and triphenylphosphine (11.5 g, 43.8 mmol) in tetrahydrofuran (150 mL). The resultant reaction mixture was stirred 22 h at ambient temperature and was concentrated in vacuo to a thick oil. Chloroform (200 mL) was added and the resultant solution was chilled to affect crystallization of diethyl 1,2-hydrazaine dicarboxylate. The precipitate was filtered and the filtrate was concentrated and further diluted with hexanes. A single crystal of triphenylphosphine oxide was added. The resultant crystals of triphenylphoshine oxide were removed by filtration and the filtrate was concentrated in vacuo and chromatographed on silica gel to afford [2-(1,3-dioxo-1,3-dihydro-isoindol-2-yloxy)-ethyl]-methyl-carbamic acid tert-butyl ester (12.8 g, 98% yield) as a colorless oil: 1H NMR (400 MHz, DMSO-d6) δ 7.86 (bs, 4 H), 8.55 (bs, H), 4.24 (t, J=5.5 Hz, 2 H), 3.50 br t, J=5.4 Hz, 2 H), 2.92 and 2.88 (br s, 3 H), 1.39 and 1.36 (br s, 9 H).

Workup

  1. customThe resultant reaction mixture
  2. concentrationwas concentrated in vacuo to a thick oil
  3. additionChloroform (200 mL) was added
  4. temperaturethe resultant solution was chilled
  5. customcrystallization of diethyl 1,2-hydrazaine dicarboxylate
  6. filtrationThe precipitate was filtered
  7. concentrationthe filtrate was concentrated
  8. additionfurther diluted with hexanes
  9. additionA single crystal of triphenylphosphine oxide was added
  10. customThe resultant crystals of triphenylphoshine oxide were removed by filtration
  11. concentrationthe filtrate was concentrated in vacuo
  12. customchromatographed on silica gel

Sources & evidence

ORD record
ord-73555e320bf8459a900137f3edabf76a
Source dataset
uspto-grants-2008_08
Patent number
US07411001B2

Reaction notes

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