Potassium Carbonate → 3'-({[(1,1-Dimethylethyl)(dimethyl)silyl]oxy}methyl)-5-fluoro-3-biphenylcarbonitrile

HRID 564473Notes

Reaction equation

HRID 564473 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([F:10])[CH:9]=1)[C:5]#[N:6].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[K+].[K+].[CH3:36][C:37]([Si:40]([CH3:53])([CH3:52])[O:41][CH2:42][C:43]1[CH:44]=[C:45](B(O)O)[CH:46]=[CH:47][CH:48]=1)([CH3:39])[CH3:38]>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:39][C:37]([Si:40]([CH3:53])([CH3:52])[O:41][CH2:42][C:43]1[CH:44]=[C:45]([C:2]2[CH:9]=[C:8]([F:10])[CH:7]=[C:4]([C:5]#[N:6])[CH:3]=2)[CH:46]=[CH:47][CH:48]=1)([CH3:36])[CH3:38]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 11776TriphenylphosphineHCID 27833303-Bromo-5-fluorobenzonitrileHCID 57813382[3-({[(1,1-Dimethylethyl)(dimethyl)silyl]oxy}methyl)phenyl]boronic acid

Product 1

HCID 578132973'-({[(1,1-Dimethylethyl)(dimethyl)silyl]oxy}methyl)-5-fluoro-3-biphenylcarbonitrile

Reagents, catalysts & solvents 2

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

Conditions

Temperature
70 °C

Procedure

3-Bromo-5-fluorobenzonitrile (5.00 g, 25.0 mmol), Pd(OAc)2 (0.15 g), PPh3 (0.60 g) and K2CO3 (5.18 g, 37.5 mmol) were dissolved in dioxane (60 mL). The mixture was heated at 70° C. for 30 min, then [3-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)phenyl]boronic acid (7.99 g, 30.0 mmol) was added. The mixture reaction was stirred at reflux overnight. The solvent was removed under reduced pressure, then diluted with CH2Cl2 (100 mL). The organic layer was washed with water (50 mL) and brine (50 mL). And the organic layer was dried over Na2SO4. The product 3′-({[(1,1-dimethylethyl) (dimethyl)silyl]oxy}methyl)-5-fluoro-3-biphenylcarbonitrile (5.10 g, 60%) was purified by flash column chromatography. 1H NMR (400 MHz, CDCl3): δ 7.67 (t, J=5.2 Hz, 1 H), 7.54-7.32 (m, 5 H), 4.81 (s, 2 H), 0.94 (s, 9 H), 0.13 (s, 6 H).

Workup

  1. customThe mixture reaction
  2. temperatureat reflux overnight
  3. customThe solvent was removed under reduced pressure
  4. additiondiluted with CH2Cl2 (100 mL)
  5. washThe organic layer was washed with water (50 mL) and brine (50 mL)
  6. dry with materialAnd the organic layer was dried over Na2SO4
  7. customThe product 3′-({[(1,1-dimethylethyl) (dimethyl)silyl]oxy}methyl)-5-fluoro-3-biphenylcarbonitrile (5.10 g, 60%) was purified by flash column chromatography

Sources & evidence

ORD record
ord-dfa991d06b2a47c8aa7fca80f78ddfe3
Source dataset
uspto-grants-2011_11
Patent number
US08067408B2

Reaction notes

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