Phthalimide → 2-(4,4-Dimethylcyclohex-2-enyl)isoindoline-1,3-dione

HRID 2280769Notes

Reaction equation

HRID 2280769 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:20]1(=[O:30])[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[C:22](=[O:29])[NH:21]1.[CH3:31][C:32]1([CH3:39])[CH2:37][CH2:36][CH:35](O)[CH:34]=[CH:33]1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1COCC1>[CH3:31][C:32]1([CH3:39])[CH2:37][CH2:36][CH:35]([N:21]2[C:22](=[O:29])[C:23]3[C:28](=[CH:27][CH:26]=[CH:25][CH:24]=3)[C:20]2=[O:30])[CH:34]=[CH:33]1

Participants

6

Reactant 4

HCID 6809PhthalimideHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 5435082-Cyclohexen-1-ol, 4,4-dimethyl-

Product 1

HCID 709821252-(4,4-Dimethylcyclohex-2-enyl)isoindoline-1,3-dioneYield 42.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Resin supported triphenylphosphine (32.7 g, 106 mmol), isoindoline-1,3-dione (17.19 g, 117 mmol), and 4,4-dimethylcyclohex-2-enol (13.4 g, 106 mmol) were combined and THF (197 mL) was added. The mixture was stirred and cooled to 0° C., then diisopropyl azodicarboxylate (21.09 mL, 107 mmol) was added drop-wise over 2 min. The reaction was stirred and allowed to warm slowly to ambient temperature overnight. The reaction mixture was filtered and then concentrated to a yellow solid under reduced pressure. Ethyl acetate (200 mL) was added and the resulting solids were filtered off again. The ethyl acetate filtrate was washed with water (100 mL), the aqueous layer extracted with ethyl acetate (100 mL), the combined organic layers were dried over anhydrous magnesium sulfate, filtered, and concentrated to an oil that was purified by silica gel chromatography (0-20% ethyl acetate/hexane) to afford 2-(4,4-dimethylcyclohex-2-enyl)isoindoline-1,3-dione (11.59 g, 45.4 mmol, 42.8% yield) as an oil. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.84 (s, 4H), 5.51-5.62 (m, 1H), 5.43 (d, J=10.15 Hz, 1H), 4.59-4.74 (m, 1H), 2.14-2.30 (m, 1H), 1.67-1.81 (m, 1H), 1.44-1.68 (m, 2H), 1.09 (s, 3H), 1.01 (s, 3H); MS (ESI) m/z 256.2 [M+1]+.

Workup

  1. stirringThe reaction was stirred
  2. temperatureto warm slowly to ambient temperature overnight
  3. filtrationThe reaction mixture was filtered
  4. concentrationconcentrated to a yellow solid under reduced pressure
  5. additionEthyl acetate (200 mL) was added
  6. filtrationthe resulting solids were filtered off again
  7. washThe ethyl acetate filtrate was washed with water (100 mL)
  8. extractionthe aqueous layer extracted with ethyl acetate (100 mL)
  9. dry with materialthe combined organic layers were dried over anhydrous magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated to an oil that
  12. customwas purified by silica gel chromatography (0-20% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-6cbb92ec8a99406e8b85e9557196af1f
Source dataset
uspto-grants-2015_09
Patent number
US09139534B2

Reaction notes

Loading…