N,N'-Dimethylethylenediamine → 2-[2-[(Acetyloxy)methyl]-3-bromophenyl]-5-(1,1-dimethylethyl)-2,3-dihydro-1H-isoindol-1-one

HRID 872148Notes

Reaction equation

HRID 872148 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[C:10](=[O:14])[NH:9][CH2:8]2)([CH3:4])([CH3:3])[CH3:2].[C:15]([O:18][CH2:19][C:20]1[C:25]([Br:26])=[CH:24][CH:23]=[CH:22][C:21]=1Br)(=[O:17])[CH3:16].C(=O)([O-])[O-].[Cs+].[Cs+].CNCCNC>[Cu](I)I.O1CCOCC1>[C:15]([O:18][CH2:19][C:20]1[C:21]([N:9]2[CH2:8][C:7]3[C:11](=[CH:12][CH:13]=[C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])[CH:6]=3)[C:10]2=[O:14])=[CH:22][CH:23]=[CH:24][C:25]=1[Br:26])(=[O:17])[CH3:16]

Participants

7

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 10796Cesium carbonateHCID 57633911HCID 57633911, compoundHCID 592164132,6-Dibromobenzyl acetate

Product 1

HCID 866979352-[2-[(Acetyloxy)methyl]-3-bromophenyl]-5-(1,1-dimethylethyl)-2,3-dihydro-1H-isoindol-1-oneYield 44.1%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
105 °C

Procedure

A 100-mL three-neck round-bottomed flask equipped with a reflux condenser, magnetic stirrer was purged with nitrogen and charged with 102c (570 mg, 3.02 mmol), 102d (1.85 g, 6.04 mmol), cesium carbonate (1.96 g, 6.04 mmol), N,N′-dimethyl-ethylenediamine (266 mg, 3.02 mmol), and 1,4-dioxane (27 mL). After bubbling nitrogen through the resulting suspension for 30 min, copper iodide (287 mg, 1.51 mmol) was added, and the reaction mixture was heated at 105° C. (oil bath temperature) for 14 h. After this time, the mixture was cooled to room temperature and filtered. The filtrate was diluted with ethyl acetate (150 mL) and water (30 mL). The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (3×50 mL). The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography (silica, 0% to 50% ethyl acetate/hexanes) to afford a 41% yield (555 mg) of 102e as an off-white solid: mp 176-178° C.; 1H NMR (300 MHz, CDCl3) δ 7.86 (d, 1H, J=8.1 Hz), 7.66 (dd, 1H, J=7.9, 1.5 Hz), 7.59 (dd, 1H, J=8.1, 1.5 Hz), 7.52 (s, 1H), 7.29 (m, 2H), 5.20 (s, 2H), 4.77 (s, 2H), 1.99 (s, 3H), 1.40 (s, 9H); MS (ESI+) m/z 416.1 (M+H).

Workup

  1. customA 100-mL three-neck round-bottomed flask equipped with a reflux condenser, magnetic stirrer
  2. customwas purged with nitrogen
  3. customAfter bubbling nitrogen through the resulting suspension for 30 min
  4. temperatureAfter this time, the mixture was cooled to room temperature
  5. filtrationfiltered
  6. additionThe filtrate was diluted with ethyl acetate (150 mL) and water (30 mL)
  7. customThe organic layer was separated
  8. extractionthe aqueous layer was extracted with ethyl acetate (3×50 mL)
  9. dry with materialThe combined organic layers were dried over sodium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by column chromatography (silica, 0% to 50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-4447f935effe4ec787d8f6833ec95ca4
Source dataset
uspto-grants-2015_03
Patent number
US08975260B2

Reaction notes

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