Phthalimide → dihydro-1H-isoindole-1,3-dione

HRID 2395131Notes

Reaction equation

HRID 2395131 reaction equation
N(C(OC)=O)=NC(OC)=O.COC1C=CC2N(C)C3C(SC=2C=1CO)=C(COCOCCOC)C(OC)=CC=3.[C:40]1(=[O:50])[NH:44][C:43](=[O:45])[C:42]2=[CH:46][CH:47]=[CH:48][CH:49]=[C:41]12.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCCC1.C(O)C.CCCCCC.C(OCC)(=O)C>[C:43]1(=[O:45])[C:42]2[CH:41]([CH2:49][CH:48]=[CH:47][CH:46]=2)[C:40](=[O:50])[NH:44]1

Participants

9

Reactant 4

HCID 6809PhthalimideHCID 11776TriphenylphosphineHCID 351621Azodicarboxylic acid dimethyl esterHCID 18972627[3,7-Dimethoxy-6-(2-methoxy-ethoxymethoxymethyl)-10-methyl-phenothiazin-4-yl]-methanol

Product 1

HCID 22048132dihydro-1H-isoindole-1,3-dione

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 3.19 g (18.32 mmol) of dimethyl azodicarboxylate in 10 ml of tetrahydrofuran was added within 4 hours under argon and while cooling with ice to a solution of 6.44 g (15.24 mmol) of [3,7-dimethoxy-6-(2-methoxy-ethoxymethoxymethyl)-10-methyl-phenothiazin-4-yl]-methanol, 2.68 g (18.11 mmol) of phthalimide and 4.40 g (16.77 mmol) of triphenylphosphine in 75 ml of tetrahydrofuran. The reaction mixture was stirred at 0° for a further 2 hours, brought slowly to room temperature and then poured into ice-water and ethyl acetate. The mixture was treated with hexane and ethanol, whereupon it was shaken vigorously. The organic phase was separated, washed with saturated sodium hydrogen carbonate solution and saturated sodium chloride solution, dried over magnesium sulphate and evaporated, and the residue was chromatographed on silica gel with ethyl acetate/hexane (1:1). After recrystallization from methanol 6.83 g (81.2%) of 2-[3,7-dimethoxy-6-(2-methoxy-ethoxymethoxymethyl)-10-methyl-phenothiazin-4-ylmethyl]-2,3:-dihydro-1H-isoindole-1,3-dione were obtained as a white solid of m.p. 135°-137°.

Workup

  1. custombrought slowly to room temperature
  2. stirringwas shaken vigorously
  3. customThe organic phase was separated
  4. washwashed with saturated sodium hydrogen carbonate solution and saturated sodium chloride solution
  5. dry with materialdried over magnesium sulphate
  6. customevaporated
  7. customthe residue was chromatographed on silica gel with ethyl acetate/hexane (1:1)
  8. customAfter recrystallization from methanol 6.83 g (81.2%) of 2-[3,7-dimethoxy-6-(2-methoxy-ethoxymethoxymethyl)-10-methyl-phenothiazin-4-ylmethyl]-2,3

Sources & evidence

ORD record
ord-717f9024314b4d5e89652a5f965866f3
Source dataset
uspto-grants-1998_09
Patent number
US05811389

Reaction notes

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