Potassium Carbonate → 2-{[3'-({[(1,1-Dimethylethyl)(dimethyl)silyl]oxy}methyl)-5-methyl-3-biphenylyl]methyl}-1H-isoindole-1,3(2H)-dione

HRID 657353Notes

Reaction equation

HRID 657353 reaction equation
C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[K+].[K+].Br[C:27]1[CH:28]=[C:29]([CH2:34][N:35]2[C:43](=[O:44])[C:42]3[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=3)[C:36]2=[O:45])[CH:30]=[C:31]([CH3:33])[CH:32]=1.[CH3:46][C:47]([Si:50]([CH3:63])([CH3:62])[O:51][CH2:52][C:53]1[CH:54]=[C:55](B(O)O)[CH:56]=[CH:57][CH:58]=1)([CH3:49])[CH3:48]>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:46][C:47]([Si:50]([CH3:63])([CH3:62])[O:51][CH2:52][C:53]1[CH:54]=[C:55]([C:27]2[CH:32]=[C:31]([CH3:33])[CH:30]=[C:29]([CH2:34][N:35]3[C:43](=[O:44])[C:42]4[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=4)[C:36]3=[O:45])[CH:28]=2)[CH:56]=[CH:57][CH:58]=1)([CH3:49])[CH3:48]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 11776TriphenylphosphineHCID 57813382[3-({[(1,1-Dimethylethyl)(dimethyl)silyl]oxy}methyl)phenyl]boronic acidHCID 578134412-[(3-bromo-5-methylphenyl)methyl]-1H-isoindole-1,3(2H)-dione

Product 1

HCID 578133262-{[3'-({[(1,1-Dimethylethyl)(dimethyl)silyl]oxy}methyl)-5-methyl-3-biphenylyl]methyl}-1H-isoindole-1,3(2H)-dioneYield 68%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

Pd(OAc)2(102.0 mg, 0.45 mmol, 0.03 eq.), PPh3 (476.4 mg, 1.82 mmol, 0.12 eq.), K2CO3(3.14 g, 22.7 mmol, 1.50 eq.) and 2-[(3-bromo-5-methylphenyl)methyl]-1H-isoindole-1,3(2H)-dione (5.00 g, 13.1 mmol, 1.00 eq.) were suspended in anhydrous 1,4-dioxane (30 mL) under nitrogen. After the mixture was heated to 60° C. for 10 min, [3-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)phenyl]boronic acid (4.84 g, 18.2 mmol, 1.20 eq.) was added. Then the reaction mixture was stirred over night at 100° C. After cooling it to room temperature, the solvent was removed under reduced pressure. Then water (25 mL) was added, extracted with CH2Cl2 twice (70 mL, 50 mL). The organic layer was washed with brine (20 mL×2), dried over anhydrous Na2SO4. After the solvent was removed, the crude product was purified on silica column chomatography, eluting with PE/EA (20:1 to 10:1), to give 4.2 g of product, 2-{[3′-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)-5-methyl-3-biphenylyl]methyl}-1H-isoindole-1,3(2H)-dione, as a colorless liquid (yield: 59%). 1H NMR (400 MHz, CDCl3) δ 0.11 (s, 6H), 0.95 (s, 9H), 2.38 (s, 3H), 4.79 (s, 2H), 4.87 (s, 2H), 7.23 (s, 1H), 7.31-7.49 (m, 6H), 7.70-7.72 (m, 2H), 7.84-7.86 (m, 2H).

Workup

  1. temperatureAfter cooling it to room temperature
  2. customthe solvent was removed under reduced pressure
  3. additionThen water (25 mL) was added
  4. extractionextracted with CH2Cl2 twice (70 mL, 50 mL)
  5. washThe organic layer was washed with brine (20 mL×2)
  6. dry with materialdried over anhydrous Na2SO4
  7. customAfter the solvent was removed
  8. customthe crude product was purified on silica column chomatography
  9. washeluting with PE/EA (20:1 to 10:1)

Sources & evidence

ORD record
ord-2931cc8ba2b04a3383a09b144f6d74f7
Source dataset
uspto-grants-2011_12
Patent number
US08071588B2

Reaction notes

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