4-Chloroanisole → 1-(4'-Fluorophenyl)-2-(4'-methoxyphenyl)-1-propanone

HRID 595353Notes

Reaction equation

HRID 595353 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6](Cl)=[CH:5][CH:4]=1.[F:10][C:11]1[CH:16]=[CH:15][C:14]([C:17](=[O:20])[CH2:18][CH3:19])=[CH:13][CH:12]=1.C(O[Na])(C)(C)C>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.COC1C=CC=C(N(C)C2C=CC=CC=2)C=1P(C1CCCCC1)C1CCCCC1>[F:10][C:11]1[CH:12]=[CH:13][C:14]([C:17](=[O:20])[CH:18]([C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[CH3:19])=[CH:15][CH:16]=1

Participants

7

Reactant 3

HCID 121674-ChloroanisoleHCID 680044-FluoropropiophenoneHCID 178418730sodium 2-methylpropan-2-olate

Product 1

HCID 1015691311-(4'-Fluorophenyl)-2-(4'-methoxyphenyl)-1-propanoneYield 80%

Reagents, catalysts & solvents 3

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

Procedure

This reaction is carried out in the same manner as the reaction in example 3. The difference is that, the reactants are p-methoxyphenyl chloride (142.8 mg, 1.0 mmol), 1-(4-fluorophenyl)-1-propanone (183.5 mg, 1.2 mmol), palladium acetate (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 (115.6 mg, 1.2 mmol) in 3 mL dry toluene at 110° C. for 18.5 h. 1-(4′-Fluorophenyl)-2-(4′-methoxyphenyl)-1-propanone (206.7 mg) was obtained with a yield of 80% as liquid. 1H NMR (300 MHz, CDCl3) δ 8.01-7.93 (m, 2H, ArH), 7.22-7.15 (m, 2H, ArH), 7.14-6.99 (m, 2H, ArH), 6.87-6.80 (m, 2H, ArH), 4.59 (q, J=7.0 Hz, 1H, CH), 3.74 (s, 3H, OCH3), 1.50 (d, J=7.0 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 198.8, 165.3 (d, J=252.7 Hz), 158.5, 133.3, 132.8 (d, J=2.6 Hz), 131.3 (d, J=8.6 Hz), 128.6, 115.4 (d, J=21.2 Hz), 114.4, 55.1, 47.0, 19.4; 19F NMR (282 MHz, CDCl3) δ −105.7; IR (neat) v (cm−1) 3071, 2974, 2932, 2869, 2837, 1682, 1598, 1514, 1505, 1455, 1409, 1372, 1336, 1302, 1247, 1180, 1157, 1114, 1101, 1035, 1006; MS (70 eV, EI) m/z (%): 259 (M++1, 1.10), 258 (M+, 6.27), 135 (100); HRMS calcd for C16H15O2F (M+): 258.1056. Found: 258.1057.

Workup

  1. customThis reaction is carried out in the same manner as the reaction in example 3
  2. customat 110° C.
  3. customfor 18.5 h

Sources & evidence

ORD record
ord-31845845732846e2943809c81bab582c
Source dataset
uspto-grants-2016_01
Patent number
US09243011B2

Reaction notes

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