1,2-Dichloroethane → 5-(4-bromophenyl)-5-(1,4-dioxan-2-ylmethyl)-5H-imidazo[2,1-a]isoindole

HRID 46179Notes

Reaction equation

HRID 46179 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH2:20][CH:21]([OH:24])[CH2:22][OH:23])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]3=[N:17][CH:18]=[CH:19][N:9]23)=[CH:4][CH:3]=1.[OH-].[Na+].Cl[CH2:28][CH2:29]Cl>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH2:20][CH:21]3[CH2:22][O:23][CH2:29][CH2:28][O:24]3)[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]3=[N:17][CH:18]=[CH:19][N:9]23)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 14798Sodium HydroxideHCID 58415410HCID 58415410, compound

Product 1

HCID 462052835-(4-bromophenyl)-5-(1,4-dioxan-2-ylmethyl)-5H-imidazo[2,1-a]isoindole

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 962WaterSolvent

Conditions

Temperature
55 °C

Procedure

To a mixture of 3-[5-(4-bromophenyl)-5H-imidazo[2,1-a]isoindol-5-yl]propane-1,2-diol (30 mg) and tetrabutylammonium bromide (30 mg) in 1,2-dichloroethane (1.125 mL) was added aqueous NaOH (35%, 1.5 mL) and heated at 55° C. for 17 h. After cooling to room temperature the reaction mixture was diluted with water and extracted with CH2Cl2 (3×). Combined organic layers were dried over Na2SO4 and concentrated. Purification by reversed phase HPLC (21×100 mm Phenomenex Gemini, 15-75% MeCN/water containing 0.05% NH4OH over 20 min at 20 mL/min) to give title compound as a slightly impure solid which was then repurified by flash chromatography using EtOAc as eluent to give desired product as a white solid. HRMS. Found, 411.0681; calcd for (M+H)+, 411.0703. 1H NMR (500 MHz, CDCl3): δ 7.89-7.83 (m, 2 H); 7.45-7.26 (m, 5 H); 7.15 (d, J=7.71 Hz, 0.5 H); 7.02 (s, 0.5 H); 7.00-6.92 (m, 3 H); 3.53-3.40 (m, 3 H); 3.36-2.97 (m, 4 H); 2.76 (dd, J=14.88, 5.92 Hz, 0.5H); 2.68 (dd, J=14.78, 5.44 Hz, 0.5 H); 2.47 (ddd, J=29.48, 14.82, 4.79 Hz, 1 H).

Workup

  1. temperatureAfter cooling to room temperature the reaction mixture
  2. extractionextracted with CH2Cl2 (3×)
  3. dry with materialCombined organic layers were dried over Na2SO4
  4. concentrationconcentrated
  5. customPurification by reversed phase HPLC (21×100 mm Phenomenex Gemini, 15-75% MeCN/water containing 0.05% NH4OH over 20 min at 20 mL/min)

Sources & evidence

ORD record
ord-4aadb8a527124e49ba502ea5e67912c7
Source dataset
uspto-grants-2013_09
Patent number
US08541595B2

Reaction notes

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