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

HRID 1821825Notes

Reaction equation

HRID 1821825 reaction equation
[OH:1][CH2:2][CH2:3][N:4]([CH3:12])[C:5](=[O:11])[O:6][C:7]([CH3:10])([CH3:9])[CH3:8].O[N:14]1[C:18](=[O:19])[C:17]2=[CH:20][CH:21]=[CH:22][CH:23]=[C:16]2[C:15]1=[O:24].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C1COCC1>[C:7]([O:6][C:5](=[O:11])[N:4]([CH2:3][CH2:2][O:1][N:14]1[C:18](=[O:19])[C:17]2[C:16](=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:15]1=[O:24])[CH3:12])([CH3:8])([CH3:9])[CH3:10]

Participants

6

Reactant 4

HCID 10665N-HydroxyphthalimideHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 545700N-(tert-Butoxycarbonyl)-N-methyl-2-aminoethanol

Product 1

HCID 59846673Tert-butyl 2-(1,3-dioxoisoindolin-2-yloxy)ethyl(methyl)carbamateYield 79%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To an ice-cold solution of tert-butyl (2-hydroxyethyl)methylcarbamate (3.0 g, 17 mmol), N-hydroxyphthalimide (2.8 g, 17 mmol) and triphenylphosphine (4.5 g, 17 mmol) in THF (90 mL) was added a solution of diethyl azodicarboxylate (3.0 mL, 19 mmol) in THF (15 mL) dropwise. The stirred reaction mixture was allowed to warm to ambient temperature. After 2 days, most of the THF was removed under reduced pressure. The residue was partitioned between CH2Cl2 (40 ml) and H2O (30 mL). The organic layer was separated and washed with saturated NaCl (20 ml), dried (Na2SO4) and concentrated under reduced pressure. Purification by column chromatography (silica gel, 50:50 hexanes/EtOAc) gave tert-butyl[2-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)oxy]ethyl]methylcarbamate (4.3 g, 79%) as a yellow oil: 1H NMR (300 MHz, CDCl3) δ1.46 (9H, s), 3.03 (3H, br s), 3.62 (2H, br s), 4.34 (2H, br s), 7.74-7.85 (4H, m).

Workup

  1. customThe stirred reaction mixture
  2. custommost of the THF was removed under reduced pressure
  3. customThe residue was partitioned between CH2Cl2 (40 ml) and H2O (30 mL)
  4. customThe organic layer was separated
  5. washwashed with saturated NaCl (20 ml)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated under reduced pressure
  8. customPurification by column chromatography (silica gel, 50:50 hexanes/EtOAc)

Sources & evidence

ORD record
ord-6ff882f24735420ea59800c39cab0ba4
Source dataset
uspto-grants-2009_10
Patent number
US07608627B2

Reaction notes

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