N-Hydroxyphthalimide → Tert-butyl 4-(1,3-dioxoisoindolin-2-yloxy)piperidine-1-carboxylate

HRID 1044821Notes

Reaction equation

HRID 1044821 reaction equation
N(C(OCC)=O)=NC(OCC)=O.[C:13]([N:20]1[CH2:25][CH2:24][CH:23]([OH:26])[CH2:22][CH2:21]1)([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14].O[N:28]1[C:32](=[O:33])[C:31]2=[CH:34][CH:35]=[CH:36][CH:37]=[C:30]2[C:29]1=[O:38].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1>[O:38]=[C:29]1[C:30]2[C:31](=[CH:34][CH:35]=[CH:36][CH:37]=2)[C:32](=[O:33])[N:28]1[O:26][CH:23]1[CH2:24][CH2:25][N:20]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:21][CH2:22]1

Participants

6

Reactant 4

HCID 10665N-HydroxyphthalimideHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylate

Product 1

HCID 21751544Tert-butyl 4-(1,3-dioxoisoindolin-2-yloxy)piperidine-1-carboxylateYield 80%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Diethyl azodicarboxylate (40% in toluene, 2.5 ml, 5.5 mmol) was added to the mixture of N-Boc-4-hydroxypiperidine (1.0 g, 5.0 mmol), N-hydroxyphthalimide (816 mg, 5.0 mmol) and triphenylphosphine (1.3 g, 5.0 mmol) in THF (10 ml) at 0° C. and stirred at room temperature for 1.5 hours. The solvent was evaporated under reduced pressure and the residue was diluted with ethyl acetate and washed with water and brine, dried (MgSO4) and evaporated under reduced pressure. The residue was purified by column chromatography on silica (EtOAc/Hexanes 30/70-70/30) to give tert-butyl 4-(1,3-dioxoisoindolin-2-yloxy)piperidine-1-carboxylate (1.37 g, 80%).

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. additionthe residue was diluted with ethyl acetate
  3. washwashed with water and brine
  4. dry with materialdried (MgSO4)
  5. customevaporated under reduced pressure
  6. customThe residue was purified by column chromatography on silica (EtOAc/Hexanes 30/70-70/30)

Sources & evidence

ORD record
ord-dfe507bfd77b45bc89439c3a43e143a9
Source dataset
uspto-grants-2013_10
Patent number
US08563732B2

Reaction notes

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