Phthalimide → 2-[(2R)-2-(4-nitrophenyl)propyl]isoindoline-1,3-dione

HRID 392928Notes

Reaction equation

HRID 392928 reaction equation
[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([C@@H:10]([CH3:13])[CH2:11]O)=[CH:6][CH:5]=1)([O-:3])=[O:2].[C:14]1(=[O:24])[NH:18][C:17](=[O:19])[C:16]2=[CH:20][CH:21]=[CH:22][CH:23]=[C:15]12.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([C@@H:10]([CH3:13])[CH2:11][N:18]2[C:14](=[O:24])[C:15]3[C:16](=[CH:20][CH:21]=[CH:22][CH:23]=3)[C:17]2=[O:19])=[CH:6][CH:5]=1)([O-:3])=[O:2]

Participants

6

Reactant 4

HCID 6809PhthalimideHCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 60078296(2R)-2-(4-nitrophenyl)propan-1-ol

Product 1

HCID 113927422-[(2R)-2-(4-nitrophenyl)propyl]isoindoline-1,3-dioneYield 97.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A 250 mL three necked round bottom flask equipped with a mechanical stirrer, addition funnel, thermometer, and a reflux condenser is charged with (2R)-2-(4-nitrophenyl)propan-1-ol (2.0 g, 11.04 mmol), phthalimide (1.62 g, 11.04 mm), triphenylphosphine (4.3 g, 16.59 mmol) and THF (50.0 mL) at room temperature. To this solution was added DEAD (2.6 mL, 16.59 mmol) over a period of 5 minutes (reaction exothermed to reflux by the end of addition). The reaction was then stirred to room temperature overnight for convenience, quenched with water (50.0 mL) and extracted organic with methylene chloride (50.0 mL). The organic layer was then dried with anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure at 50° C. to an oil (11.62 g). Plug filtration of the oil over silica gel with 1:1 ethyl acetate/hexane (470.0 mL) and subsequent concentration of the fractions containing product afforded a light yellow precipitate. The precipitate was then dried in a house vacuum at 40° C. to provide 2-[(2R)-2-(4-nitrophenyl)propyl]isoindoline-1,3-dione (3.32 g, 96.9%); 1H nmr (CDCl3, 300 MHz) δ 1.50 (d, 3H, J=6.74 Hz), 3.45 (m, 1H), 3.89-3.95 (m, 2H), 7.5 (d, 2H), 7.67 (m, 2H), 7.68 (m, 2H), 8.10 (d, 2H); 13C nmr (CDCl3, 300 MHz δ 19.21, 38.90, 44.45, 123.59, 123.99, 128.50, 131.86, 134.35, 151.13, 168.34.

Workup

  1. customreaction exothermed
  2. temperatureto reflux by the end of addition)
  3. customquenched with water (50.0 mL)
  4. extractionextracted organic with methylene chloride (50.0 mL)
  5. dry with materialThe organic layer was then dried with anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure at 50° C. to an oil (11.62 g)
  8. filtrationPlug filtration of the oil over silica gel
  9. concentrationwith 1:1 ethyl acetate/hexane (470.0 mL) and subsequent concentration of the fractions
  10. additioncontaining product
  11. customafforded a light yellow precipitate
  12. customThe precipitate was then dried in a house vacuum at 40° C.

Sources & evidence

ORD record
ord-12c9be1b3ad946d5ad538f3945040261
Source dataset
uspto-grants-2004_10
Patent number
US06803484B2

Reaction notes

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