1,10-Phenanthroline → 7-Methyl-5-(pyridin-4-ylmethoxy)-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-isoindol-1-one

HRID 2427540Notes

Reaction equation

HRID 2427540 reaction equation
I[C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([CH3:11])[CH:10]=1)[C:7](=[O:12])[N:6]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][C:21]([F:24])([F:23])[F:22])=[CH:16][CH:15]=1)[CH2:5]2.[N:25]1[CH:30]=[CH:29][C:28]([CH2:31][OH:32])=[CH:27][CH:26]=1.C(=O)([O-])[O-].[Cs+].[Cs+].N1C2C(=CC=C3C=2N=CC=C3)C=CC=1>C1(C)C=CC=CC=1.[Cu]I>[CH3:11][C:9]1[CH:10]=[C:2]([O:32][CH2:31][C:28]2[CH:29]=[CH:30][N:25]=[CH:26][CH:27]=2)[CH:3]=[C:4]2[C:8]=1[C:7](=[O:12])[N:6]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][C:21]([F:22])([F:24])[F:23])=[CH:16][CH:15]=1)[CH2:5]2

Participants

7

Reactant 4

HCID 13181,10-PhenanthrolineHCID 10796Cesium carbonateHCID 114724-HydroxymethylpyridineHCID 579493925-Iodo-7-methyl-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-isoindol-1-one

Product 1

HCID 579497427-Methyl-5-(pyridin-4-ylmethoxy)-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-isoindol-1-oneYield 47%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 1140TolueneSolvent

Procedure

To a solution of 5-Iodo-7-methyl-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-isoindol-1-one (100 mg, 0.22 mmol) in toluene (3 ml), pyridin-4-yl-methanol (26.4 mg, 0.24 mmol), copper(I) iodide (40 mg, 0.022 mmol), cesium carbonate (143 mg, 0.44 mmol), and 1,10-phenanthroline (7.9 mg, 0.044 mmol) were added. The resulting mixture was refluxed overnight, After cooling, the mixture was filtered through Celite® and concentrated. Column chromatography (80% EtOAc/Hexanes to 10% MeOH/EtOAc) provided the title compound as a yellow oil (44.3 mg, 47%). 1H NMR (300 MHz, CDCl3): δ 8.56 (br, 2H), 7.31-7.36 (m, 3H), 7.16-7.20 (m, 3H), 6.83 (s, 1H), 6.75 (s, 1H), 5.14 (s, 2H), 4.75 (s, 2H), 4.19 (s, 2H), 2.74 (s, 3H). GTPγS (0.0645).

Workup

  1. temperatureThe resulting mixture was refluxed overnight
  2. temperatureAfter cooling
  3. filtrationthe mixture was filtered through Celite®
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-1a2210b37f9b412d9cf081d16a19c209
Source dataset
uspto-grants-2011_06
Patent number
US07968570B2

Reaction notes

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