Benzene → 1,10a-Dihydropyrrolo[1,2-b]isoquinoline-3,10[2H,5H]-dione

HRID 2304548Notes

Reaction equation

HRID 2304548 reaction equation
[CH2:1]([N:8]1[CH2:12][CH:11](C(O)=O)[CH2:10][C:9]1=[O:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(Cl)(Cl)=O.[Al+3].[Cl-].[Cl-].[Cl-].[OH2:25].[CH:26]1C=CC=CC=1>N1C=CC=CC=1.CCOCC.CC(C)=O>[CH2:11]1[CH:12]2[N:8]([CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][C:7]=3[C:26]2=[O:25])[C:9](=[O:16])[CH2:10]1

Participants

9

Reactant 5

HCID 241BenzeneHCID 962WaterHCID 24386Thionyl ChlorideHCID 990241-Benzyl-5-oxo-pyrrolidine-3-carboxylic acidHCID 6451240Aluminum(III) Chloride

Product 1

HCID 131500811,10a-Dihydropyrrolo[1,2-b]isoquinoline-3,10[2H,5H]-dione

Reagents, catalysts & solvents 3

HCID 1049PyridineCatalystHCID 180AcetoneSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
67.5 °C

Procedure

A mixture of N-benzyl-pyrrolidin-2-one-4-carboxylic acid (3.7 mmol, 860 mg), thionyl chloride (8 mL) and pyridine (1 drop) was heated at 65-70° C. for 20 min. The pale yellow solution was evaporated in vacuo. The resulting acid chloride was dissolved in benzene (16 mL) and added within 30 min to a suspension of AlCl3 (122 mmol, 16.3 g) in benzene (40 mL). The suspension was heated at 55° C. for 30 min and then at 65° C. for 5 min. The mixture was then cooled and hydrolyzed with a minimum amount of water and ice. The aqueous phase was extracted with CH2Cl2 (2×30 mL). The organic phase was washed with water, aqueous NaOH (1 N) and more water, dried with Na2SO4 and concentrated in vacuo to give an oil. Acetone and ether was added to the oil and precipitate formed overnight. The precipitate was filtered and dried in vacuo to give 1,2,3,5,10,10a-hexahydropyrrolo[1,2-b]isoquinolin-3,10-dione acid as a yellow solid (557 mg): mp 105-107° C. (lit. mp 107-108° C.); 1H NMR (300 MHz) δ 8.09 (dd, J=7.8, 0.9 Hz, 1 H), 7.60 (td, J=7.5, 1.3 Hz, 1 H), 7.42 (t, J=7.6 Hz, 1 H), 7.33 (d, J=7.7 Hz, 1 H), 5.28 (d, J=17.5 Hz, 1 H), 4.37 (d, J=17.5 Hz, 1 H), 4.32 (m, 1 H), 2.50 (m, 4 H); 13C NMR (75 MHz) δ 194.03, 173.79, 139.62, 134.36, 130.08, 127.71, 127.59, 126.42, 61.64, 41.32, 29.78, 20.45.

Workup

  1. customThe pale yellow solution was evaporated in vacuo
  2. dissolutionThe resulting acid chloride was dissolved in benzene (16 mL)
  3. temperatureThe suspension was heated at 55° C. for 30 min
  4. temperatureThe mixture was then cooled
  5. extractionThe aqueous phase was extracted with CH2Cl2 (2×30 mL)
  6. washThe organic phase was washed with water, aqueous NaOH (1 N) and more water
  7. dry with materialdried with Na2SO4
  8. concentrationconcentrated in vacuo
  9. customto give an oil
  10. customformed overnight
  11. filtrationThe precipitate was filtered
  12. customdried in vacuo

Sources & evidence

ORD record
ord-2a2e699d5a3f43979f52934f186a6527
Source dataset
uspto-grants-2002_08
Patent number
US06436954B1

Reaction notes

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