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

HRID 1895897Notes

Reaction equation

HRID 1895897 reaction equation
N(C(OCC)=O)=NC(OCC)=O.[OH:13][CH:14]1[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]1.O[N:28]1[C:36](=[O:37])[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[C:29]1=[O:38].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCCC1>[O:38]=[C:29]1[C:30]2[C:35](=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:36](=[O:37])[N:28]1[O:13][CH:14]1[CH2:15][CH2:16][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:18][CH2:19]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 45%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Diethyl azodicarboxylate (17.4 g, 100 mmol) was added to a solution of tert-butyl 4-hydroxypiperidine-1-carboxylate (7.50 g, 37.3 mmol), 2-hydroxyisoindoline-1,3-dione (6.08 g, 37.3 mmol) and triphenylphosphine (19.6 g, 74.6 mmol) in tetrahydrofuran (100 ml) at 0° C. The reaction mixture was stirred at room temperature for 17 hours and concentrated in vacuo. The residue was purified by column chromatography (ethyl acetate/petroleum ether: 5/95 to 12.5/87.5) to give tert-butyl 4-(1,3-dioxoisoindolin-2-yloxy)piperidine-1-carboxylate (5.81 g, 45%) as a white solid: LCMS: 247 [M+1]+.

Workup

  1. concentrationconcentrated in vacuo
  2. customThe residue was purified by column chromatography (ethyl acetate/petroleum ether: 5/95 to 12.5/87.5)

Sources & evidence

ORD record
ord-a1e2198142d944e4b339783eebaa59af
Source dataset
uspto-grants-2013_08
Patent number
US08518934B2

Reaction notes

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