N-Hydroxyphthalimide → 1,1-Dimethylethyl (2R)-2-((1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)oxy)propanoate

HRID 708403Notes

Reaction equation

HRID 708403 reaction equation
[OH:1][N:2]1[C:6](=[O:7])[C:5]2=[CH:8][CH:9]=[CH:10][CH:11]=[C:4]2[C:3]1=[O:12].C(=O)([O-])[O-].[K+].[K+].Cl[C@@H:20]([CH3:28])[C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22]>CN(C=O)C.CCOC(C)=O.[Li+].[Cl-]>[O:7]=[C:6]1[C:5]2[C:4](=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:3](=[O:12])[N:2]1[O:1][C@H:20]([CH3:28])[C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22]

Participants

6

Reactant 3

HCID 10665N-HydroxyphthalimideHCID 11430Potassium CarbonateHCID 11084226(S)-tert-Butyl 2-chloropropanoate

Product 1

HCID 108808241,1-Dimethylethyl (2R)-2-((1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)oxy)propanoateYield 85%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 131733757EtOAc LiClSolvent

Conditions

Temperature
40 °C

Procedure

To a slurry of N-hydroxyphthalimide (3.71 g, 22.1 mmol) and potassium carbonate (4.58 g, 33.1 mmol) in DMF (55 mL) was added (S)-tert-butyl 2-chloropropanoate (4.30 g, 24.3 mmol). After 72 h of stirring, the slurry was heated to 40° C. for an additional 16 h, at which point it was diluted with EtOAc/LiCl (5% aq) and the layers were separated. The aqueous layer was extracted with EtOAc (2×) and the combined organic layers were washed with LiCl (5% aq), brine, dried over Na2SO4 and concentrated in vacuo, affording the title compound (5.45 g, 85%) as an off-white solid. LCMS: Rt=0.88 min, m/z=313.9 (M+23) Method 2m_acidic.

Workup

  1. customthe layers were separated
  2. extractionThe aqueous layer was extracted with EtOAc (2×)
  3. washthe combined organic layers were washed with LiCl (5% aq), brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-04d3f3fead9c47ab9cc772cb1e6b1b7d
Source dataset
uspto-grants-2015_11
Patent number
US09174978B2

Reaction notes

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