1-Phenyl-1-propanone → Alpha-(4-methoxyphenyl)propiophenone

HRID 595348Notes

Reaction equation

HRID 595348 reaction equation
C(O[Na])(C)(C)C.[CH3:7][O:8][C:9]1[CH:14]=[CH:13][C:12](Cl)=[CH:11][CH:10]=1.[C:16]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)(=[O:19])[CH2:17][CH3:18]>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2].COC1C=CC=C(N(C)C2C=CC=CC=2)C=1P(C1CCCCC1)C1CCCCC1>[CH3:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([CH:17]([CH3:18])[C:16]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[O:19])=[CH:11][CH:10]=1

Participants

7

Reactant 3

HCID 71481-Phenyl-1-propanoneHCID 121674-ChloroanisoleHCID 178418730sodium 2-methylpropan-2-olate

Product 1

HCID 11096728Alpha-(4-methoxyphenyl)propiophenoneYield 87.1%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 71725627(2-Dicyclohexylphosphino-3-methoxy-N-methyl-N-phenylbenzenamineCatalystHCID 1140TolueneSolvent2×

Procedure

To a flame-dried and nitrogen filled Schlenk vessel were added Pd(OAc)2 (6.7 mg, 0.030 mmol), 2-Methoxy-6-(N-methyl-N-phenyl-amino)phenyl(dicyclohexyl)phosphine (18.3 mg, 0.045 mmol), t-BuONa (115.4 mg, 1.2 mmol), and p-methoxyphenyl chloride (142.1 mg, 1.0 mmol)) in 1.5 mL of toluene sequentially. After being stirred for about 2 min at room temperature, propiophenone (160.9 mg, 1.2 mmol) in 1.5 mL of toluene were added. The resulting mixture was heated at 110° C. with a preheated oil bath. After 17.5 h, the reaction was complete as monitored by GC. The reaction mixture was then cooled and quenched with 10 mL of Et2O. After transferring the mixture into separatory funnel, the reactor was further washed with 10 mL of Et2O and 10 mL of HCl aqueous solution (5%). The combined mixture was extracted with Et2O (10 mL×2), washed with 20 mL of saturated NaHCO3 aqueous solution, and dried over anhydrous Na2SO4. Filtration, evaporation, and purification by chromatography (petroleum ether/ethyl acetate=80/1) on silica gel afforded 2-(4′-Methoxyphenyl)-1-phenyl-1-propanone (209.4 mg, 87%) as a liquid: 1H NMR (300 MHz, CDCl3) δ 8.00-7.92 (m, 2H, ArH), 7.52-7.43 (m, 1H, ArH), 7.42-7.35 (m, 2H, ArH), 7.24-7.18 (m, 2H, ArH), 6.86-6.80 (m, 2H, ArH), 4.65 (q, J=6.9 Hz, 1H, CH), 3.75 (s, 3H, OCH3), 1.52 (d, J=6.9 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 200.5, 158.4, 136.5, 133.4, 132.6, 128.73, 128.69, 138.4, 114.3, 55.1, 46.9, 19.5; IR (neat) v (cm−1) 3061, 2972, 2931, 2836, 1682, 1609, 1596, 1511, 1448, 1302, 1248, 1221, 1178, 1034, 1002; MS (70 eV, EI) m/z (%): 240 (M+, 4.46), 135 (100).

Workup

  1. customTo a flame-dried
  2. temperatureThe resulting mixture was heated at 110° C. with a preheated oil bath
  3. waitAfter 17.5 h
  4. temperatureThe reaction mixture was then cooled
  5. customquenched with 10 mL of Et2O
  6. washthe reactor was further washed with 10 mL of Et2O and 10 mL of HCl aqueous solution (5%)
  7. extractionThe combined mixture was extracted with Et2O (10 mL×2)
  8. washwashed with 20 mL of saturated NaHCO3 aqueous solution
  9. dry with materialdried over anhydrous Na2SO4
  10. filtrationFiltration, evaporation, and purification by chromatography (petroleum ether/ethyl acetate=80/1) on silica gel

Sources & evidence

ORD record
ord-7f19a552289f4aaaa105c31fc42fbb0c
Source dataset
uspto-grants-2016_01
Patent number
US09243011B2

Reaction notes

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