Toluene → 1-Benzyloxy-2-(4-fluorophenyl)-4-ethyl-5-[(3-cyanopropyl)oxy]-benzene

HRID 1835595Notes

Reaction equation

HRID 1835595 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5](B(O)O)=[CH:4][CH:3]=1.[CH2:11]([O:18][C:19]1[CH:24]=[C:23]([O:25][CH2:26][CH2:27][CH2:28][C:29]#[N:30])[C:22]([CH2:31][CH3:32])=[CH:21][C:20]=1Br)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>C(O)C.C(OCC)(=O)C>[CH2:11]([O:18][C:19]1[CH:24]=[C:23]([O:25][CH2:26][CH2:27][CH2:28][C:29]#[N:30])[C:22]([CH2:31][CH3:32])=[CH:21][C:20]=1[C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=1)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 23501857HCID 23501857, compound

Product 1

HCID 235018421-Benzyloxy-2-(4-fluorophenyl)-4-ethyl-5-[(3-cyanopropyl)oxy]-benzeneYield 70.5%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-fluorobenzene boronic acid (1.14 g) was dissolved in ethanol (7 mL). To this was added 1-(benzyloxy)-2-bromo-4-ethyl-5-[(3-cyanopropyl)oxy]-benzene (1.5 g), toluene (20 mL), tetrakis-triphenylphosphine palladium (470 mg), and 2M sodium carbonate solution (6.1 mL). The resulting mixture was heated to reflux and held there for 24 hours. The solution was cooled, diluted with ethyl acetate, and the layers separated. The organic layer was washed with saturated ammonium chloride, dried over magnesium sulfate, filtered, and concentrated to afford a green oil. This was purified by flash chromatography on silica using hexane/ethyl acetate (9:1). The resulting fractions were concentrated under vacuum to afford 1-Benzyloxy-2-(4-fluorophenyl)-4-ethyl-5-[(3-cyanopropyl)oxy]-benzene (1.1 g) as a clear oil. NMR (CDCl3): 1.18, t (3H); 2.15, m (2H); 2.59, m (4H); 4.06, t (2H); 5.00, s (2H); 6.53, s (1H); 7.06, t (2H); 7.09, s (1H); 7.30, m (5H); 7.49, d of d (2H).

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureto reflux
  3. temperatureThe solution was cooled
  4. customthe layers separated
  5. washThe organic layer was washed with saturated ammonium chloride
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto afford a green oil
  10. customThis was purified by flash chromatography on silica
  11. concentrationThe resulting fractions were concentrated under vacuum

Sources & evidence

ORD record
ord-bf077facdb1b4156b1fcae14e731b3c4
Source dataset
uspto-grants-2004_08
Patent number
US06770259B2

Reaction notes

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