2-Phthalimidoacetaldehyde Diethyl Acetal → 2-(7-Bromoquinolin-3-yl)isoindoline-1,3-dione

HRID 1525924Notes

Reaction equation

HRID 1525924 reaction equation
C(O[CH:4](OCC)[CH2:5][N:6]1[C:14](=[O:15])[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7]1=[O:16])C.[NH2:20][C:21]1[CH:28]=[C:27]([Br:29])[CH:26]=[CH:25][C:22]=1[CH:23]=O.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[Br:29][C:27]1[CH:28]=[C:21]2[C:22]([CH:23]=[C:5]([N:6]3[C:7](=[O:16])[C:8]4[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=4)[C:14]3=[O:15])[CH:4]=[N:20]2)=[CH:25][CH:26]=1

Participants

5

Reactant 3

HCID 3152862-Phthalimidoacetaldehyde Diethyl AcetalHCID 521998p-Toluenesulfonic acid monohydrateHCID 179145982-Amino-4-bromobenzaldehyde

Product 1

HCID 690851162-(7-Bromoquinolin-3-yl)isoindoline-1,3-dioneYield 45.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of 2-(2,2-diethoxyethyl)isoindoline-1,3-dione (3.16 g, 12.00 mmol), 2-amino-4-bromobenzaldehyde (2 g, 10.00 mmol) and p-toluenesulfonic acid monohydrate (1.902 g, 10.00 mmol) in toluene (60 mL) was heated under reflux using Dean-Stark apparatus overnight. A very dark/black solid precipitated overnight and was collected, washed with toluene and hexanes, then dissolved in chloroform fortified with DMF. The mixture was washed with aq. NaHCO3 solution (×2), ensuring any precipitate was dissolved in additional chloroform during separation. The organic layer was dried (sodium sulfate) and evaporated onto silica gel. Purification by flash chromatography (0-2% methanol in dichloromethane) afforded the title compound (1.6 g, 45%). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.05 (d, 1 H), 8.57 (d, J=2.3 Hz, 1 H), 8.35 (d, J=1.8 Hz, 1 H), 8.11 (d, J=8.6 Hz, 1 H), 8.09-8.02 (m, 2 H), 8.02-7.93 (m, 2 H), 7.87 (dd, J=1.9, 8.7 Hz, 1 H).

Workup

  1. temperaturewas heated
  2. temperatureunder reflux
  3. customDean-Stark apparatus overnight
  4. customA very dark/black solid precipitated overnight
  5. customwas collected
  6. washwashed with toluene and hexanes
  7. dissolutiondissolved in chloroform
  8. washThe mixture was washed with aq. NaHCO3 solution (×2)
  9. dissolutionwas dissolved in additional chloroform during separation
  10. dry with materialThe organic layer was dried (sodium sulfate)
  11. customevaporated onto silica gel
  12. customPurification by flash chromatography (0-2% methanol in dichloromethane)

Sources & evidence

ORD record
ord-7940a6fb4f9b45a4b5930f9f78f68be4
Source dataset
uspto-grants-2015_07
Patent number
US09084794B2

Reaction notes

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