N-Hydroxyphthalimide → 2-(2-Thienylmethoxy)-1H-isoindole-1,3(2H)-dione

HRID 602610Notes

Reaction equation

HRID 602610 reaction equation
[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][OH:7].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.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].CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][O:7][N:28]1[C:29](=[O:38])[C:30]2=[CH:37][CH:36]=[CH:35][CH:34]=[C:31]2[C:32]1=[O:33]

Participants

6

Reactant 4

HCID 10665N-HydroxyphthalimideHCID 11776TriphenylphosphineHCID 694672-ThiophenemethanolHCID 5462977Diethyl azodicarboxylate

Product 1

HCID 107064032-(2-Thienylmethoxy)-1H-isoindole-1,3(2H)-dioneYield 13.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of 2-thiophenemethanol (4.15 mL, 43.64 mmol), triphenylphosphine (12.59 g, 48.01 mmol) and N-hydroxyphthalimide (7.83 g, 48.01 mmol) in THF (120 mL) at 0° C. was added dropwise diethylazodicarboxylate (7.56 mL, 48.01 mmol) in THF (20 mL). The reaction mixture was allowed to stir for 15 h after which the solvent was removed under vacuum to dryness. Et2O (50 mL) was added to triturate the triphenylphosphine oxide and diethylhydrazinedicarboxylate, which was filtered off and washed with a little Et2O. The ethereal solution was concentrated under vacuum to give a residue which was filtered through a pad of silica (eluting with EtOAc/PE, 3:7). Removal of the solvent under reduced pressure afforded N-(thiophen-2-ylmethoxy)phthalimide (1.50 g, 13%), as a pale yellow solid.

Workup

  1. customwas removed under vacuum to dryness
  2. additionEt2O (50 mL) was added
  3. customto triturate the triphenylphosphine oxide and diethylhydrazinedicarboxylate, which
  4. filtrationwas filtered off
  5. washwashed with a little Et2O
  6. concentrationThe ethereal solution was concentrated under vacuum
  7. customto give a residue which
  8. filtrationwas filtered through a pad of silica (eluting with EtOAc/PE, 3:7)
  9. customRemoval of the solvent under reduced pressure

Sources & evidence

ORD record
ord-251204b0c1e743e7a089cdb63f0f4efc
Source dataset
uspto-grants-2011_03
Patent number
US07906538B2

Reaction notes

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