Potassium Carbonate → (S)-(5-(methylsulfonyl)-2-(1,1,1-trifluoropropan-2-yloxy)phenyl)(5-phenylisoindolin-2-yl)methanone

HRID 225745Notes

Reaction equation

HRID 225745 reaction equation
I[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH2:7][N:6]([C:11]([C:13]1[CH:18]=[C:17]([S:19]([CH3:22])(=[O:21])=[O:20])[CH:16]=[CH:15][C:14]=1[O:23][C@@H:24]([CH3:29])[C:25]([F:28])([F:27])[F:26])=[O:12])[CH2:5]2.[C:30]1(B(O)O)[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH3:22][S:19]([C:17]1[CH:16]=[CH:15][C:14]([O:23][C@@H:24]([CH3:29])[C:25]([F:26])([F:28])[F:27])=[C:13]([C:11]([N:6]2[CH2:5][C:4]3[C:8](=[CH:9][CH:10]=[C:2]([C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)[CH:3]=3)[CH2:7]2)=[O:12])[CH:18]=1)(=[O:20])=[O:21]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 57753242(5-Iodo-1,3-dihydro-isoindol-2-yl)-[5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl ethoxy)-phenyl]-methanone

Product 1

HCID 11569401(S)-(5-(methylsulfonyl)-2-(1,1,1-trifluoropropan-2-yloxy)phenyl)(5-phenylisoindolin-2-yl)methanoneYield 50%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 0.19 mmol (5-Iodo-1,3-dihydro-isoindol-2-yl)-[5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-methanone (Example C3) in 1 ml DMF under argon was added successively 0.018 mmol tetrakistriphenylphosphine, 0.28 mmol phenyl boronic acid and 0.56 mmol potassium carbonate. The reaction mixture was heated at 120° C. for 2 hours then cooled to room temperature and filtered. The filtrate was evaporated to dryness and the residue was treated with sat. NaCl. The resulting mixture was extracted 3 times with dichloromethane. The organics phases were dried over sodium sulfate and evaporated. The crude compound was purified on a 10 g of Si-Amine cartridge: n-Heptane/Ethylacetate to provide the title compound (50%). Off-white solid. MS (m/e): 490.0 [M+H]+, 100%).

Workup

  1. temperaturethen cooled to room temperature
  2. filtrationfiltered
  3. customThe filtrate was evaporated to dryness
  4. additionthe residue was treated with sat. NaCl
  5. extractionThe resulting mixture was extracted 3 times with dichloromethane
  6. dry with materialThe organics phases were dried over sodium sulfate
  7. customevaporated
  8. customThe crude compound was purified on a 10 g of Si-Amine cartridge

Sources & evidence

ORD record
ord-ec74c42f9386439fae34cf8ede54bba6
Source dataset
uspto-grants-2009_07
Patent number
US07557114B2

Reaction notes

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