Sodium Carbonate → 7-Methyl-5-(5-methyl-pyridin-3-yl)-2-(4-phenoxy-benzyl)-2,3-dihydro-isoindol-1-one

HRID 2427516Notes

Reaction equation

HRID 2427516 reaction equation
Br[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]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[CH:16][CH:15]=1)[CH2:5]2.[CH3:27][C:28]1[CH:29]=[N:30][CH:31]=[C:32](B(O)O)[CH:33]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:11][C:9]1[CH:10]=[C:2]([C:32]2[CH:31]=[N:30][CH:29]=[C:28]([CH3:27])[CH:33]=2)[CH:3]=[C:4]2[C:8]=1[C:7](=[O:12])[N:6]([CH2:13][C:14]1[CH:15]=[CH:16][C:17]([O:20][C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=3)=[CH:18][CH:19]=1)[CH2:5]2

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27627085-Methylpyridine-3-boronic acidHCID 116039005-Bromo-7-methyl-2-(4-phenoxybenzyl)-2,3-dihydroisoindol-1-one

Product 1

HCID 579494527-Methyl-5-(5-methyl-pyridin-3-yl)-2-(4-phenoxy-benzyl)-2,3-dihydro-isoindol-1-oneYield 63.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
110 °C

Procedure

5-Bromo-7-methyl-2-(4-phenoxy-benzyl)-2,3-dihydro-isoindol-1-one (100.0 mg, 0.24 mmol), 3-methylpyridine-5-boronic acid (67.1 mg, 0.49 mmol), 2M sodium carbonate (1 mL) and Pd(PPh3)4 (37.0 mg, 0.045 mmol) were suspended in DME (1 mL), and the mixture was heated to 110° C. After 15 hours, the reaction mixture was cooled to room temperature. The cooled reaction mixture was partitioned between ethyl acetate and water. The aqueous phase was extracted with ethyl acetate and the combined organic phase was washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The product was purified by column chromatography (30-35% EtOAc in hexanes) to provide the title compound as an off-white gum (64 mg, 62%.) 1H NMR (300 MHz, CDCl3): δ 8.66 (d, 1H), 8.47 (d, 1H), 7.70 (s, 1H), 7.28-7.41 (m, 6H), 7.12 (t, 1H), 6.98-7.03 (m, 4H), 4.79 (s, 2H), 4.33 (s, 2H), 2.85 (s, 3H), 2.44 (s, 3H).

Workup

  1. temperaturethe reaction mixture was cooled to room temperature
  2. customThe cooled reaction mixture
  3. customwas partitioned between ethyl acetate and water
  4. extractionThe aqueous phase was extracted with ethyl acetate
  5. washthe combined organic phase was washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe product was purified by column chromatography (30-35% EtOAc in hexanes)

Sources & evidence

ORD record
ord-ff075ffc9e3545088f87c584cb4a870b
Source dataset
uspto-grants-2011_06
Patent number
US07968570B2

Reaction notes

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