N-Hydroxyphthalimide → (S)-3-(1,3-Dioxo-1,3-dihydro-isoindol-2-yloxy)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1895936Notes

Reaction equation

HRID 1895936 reaction equation
N(C(OCC)=O)=NC(OCC)=O.[C:13]([O:17][C:18]([N:20]1[CH2:24][CH2:23][C@@H:22]([OH:25])[CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14].O[N:27]1[C:35](=[O:36])[C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[C:28]1=[O:37].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCCC1>[O:37]=[C:28]1[C:29]2[C:34](=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:35](=[O:36])[N:27]1[O:25][C@H:22]1[CH2:23][CH2:24][N:20]([C:18]([O:17][C:13]([CH3:16])([CH3:14])[CH3:15])=[O:19])[CH2:21]1

Participants

6

Reactant 4

HCID 10665N-HydroxyphthalimideHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 6544479tert-Butyl (3R)-3-hydroxypyrrolidine-1-carboxylate

Product 1

HCID 59704735(S)-3-(1,3-Dioxo-1,3-dihydro-isoindol-2-yloxy)-pyrrolidine-1-carboxylic acid tert-butyl esterYield 40.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Diethyl azodicarboxylate (17.4 g, 100 mmol) was added to a solution of (R)-tert-butyl-3-hydroxypyrrolidin-1-carboxylate (9.40 g, 50 mmol), 2-hydroxyisoindoline-1,3-dione (8.16 g, 50 mmol) and triphenylphosphine (26.2 g, 100 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 (S)-tert-butyl 3-(1,3-dioxoisoin dolin-2-yloxy)pyrrolidin-1-carboxylate (6.74 g, 20%) as a white solid: LCMS: 277 [M−55]+

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-7861ac487c90439696e50fea41868431
Source dataset
uspto-grants-2013_08
Patent number
US08518934B2

Reaction notes

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