Potassium Carbonate → 3'-({[(1,1-Dimethylethyl)(dimethyl)silyl]oxy}methyl)-2-fluoro-3-biphenylcarboxamide

HRID 657351Notes

Reaction equation

HRID 657351 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[C:28]([F:36])=[C:29]([CH:33]=[CH:34][CH:35]=1)[C:30]([NH2:32])=[O:31].[CH3:37][C:38]([Si:41]([CH3:54])([CH3:53])[O:42][CH2:43][C:44]1[CH:45]=[C:46](B(O)O)[CH:47]=[CH:48][CH:49]=1)([CH3:40])[CH3:39]>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:40][C:38]([Si:41]([CH3:54])([CH3:53])[O:42][CH2:43][C:44]1[CH:45]=[C:46]([C:27]2[CH:35]=[CH:34][CH:33]=[C:29]([C:30]([NH2:32])=[O:31])[C:28]=2[F:36])[CH:47]=[CH:48][CH:49]=1)([CH3:37])[CH3:39]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 11776TriphenylphosphineHCID 442031023-Bromo-2-fluorobenzamideHCID 57813382[3-({[(1,1-Dimethylethyl)(dimethyl)silyl]oxy}methyl)phenyl]boronic acid

Product 1

HCID 578133053'-({[(1,1-Dimethylethyl)(dimethyl)silyl]oxy}methyl)-2-fluoro-3-biphenylcarboxamideYield 63%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
80 °C

Procedure

Pd(OAc)2 (123.6 mg, 0.55 mmol), PPh3 (557.5 mg, 2.2 mmol), K2CO3 (3.8 g, 27.5 mmol) and 3-bromo-2-fluorobenzamide (4.0 g, 18.4 mmol) were suspended in 1,4-dioxane (30 mL). After the mixture was heated to 80° C. for 15 min, [3-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)phenyl]boronic acid (5.9 g, 22.0 mmol) was added. Then the reaction mixture was stirred over night at 100° C. After cooling to room temperature, the solvent was removed under reduced pressure. The residue was dissolved in CH2Cl2 (50 mL), then was washed with water (20 mL), brine (20 mL), and dried over Na2SO4. After the solvent was removed, the crude product was purified on an Al2O3 column chomatography, eluting with CH2Cl2/CH3OH (300:1). 3′-({[(1,1-Dimethylethyl)(dimethyl)silyl]oxy}methyl)-2-fluoro-3-biphenylcarboxamide, was obtained (4.1 g, yield: 63%). 1H NMR (400 MHz, CDCl3) δ 0.12 (s, 6H), 0.95 (s, 9H), 4.81 (s, 2H), 7.25-8.12 (m, 7H).

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe solvent was removed under reduced pressure
  3. dissolutionThe residue was dissolved in CH2Cl2 (50 mL)
  4. washwas washed with water (20 mL), brine (20 mL)
  5. dry with materialdried over Na2SO4
  6. customAfter the solvent was removed
  7. customthe crude product was purified on an Al2O3 column chomatography
  8. washeluting with CH2Cl2/CH3OH (300:1)

Sources & evidence

ORD record
ord-8f6b07a1492642e1a178505b44044591
Source dataset
uspto-grants-2011_12
Patent number
US08071588B2

Reaction notes

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